Skip to main content

Advertisement

SpringerLink
Log in

Cardiovascular Exosomes and MicroRNAs in Cardiovascular Physiology and Pathophysiology

  • Review
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Cardiac exosomes mediate cell-to-cell communication, stimulate or inhibit the activities of target cells, and affect myocardial hypertrophy, injury and infarction, ventricular remodeling, angiogenesis, and atherosclerosis. The exosomes that are released in the heart from cardiomyocytes, vascular cells, fibroblasts, and resident stem cells are hypoimmunogenic, are physiologically more stable than cardiac cells, can circulate in the body, and are able to cross the blood–brain barrier. Exosomes utilize three mechanisms for cellular communication: (1) internalization by cells, (2) direct fusion to the cell membrane, and (3) receptor-ligand interactions. Cardiac exosomes transmit proteins, mRNA, and microRNAs to other cells during both physiological and pathological process. Cardiac-specific exosome miRNAs can regulate the expression of sarcomeric genes, ion channel genes, autophagy, anti-apoptotic and anti-fibrotic activity, and angiogenesis. This review discusses the role of exosomes and microRNAs in normal myocardium, myocardial injury and infarction, atherosclerosis, and the importance of circulating microRNAs as biomarkers of cardiac disease.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Due to space limitations, not all excellent papers on cardiac exosomes could be listed in the bibliography

  1. Colombo, M., Raposo, G., & Thery, C. (2014). Biogenesics, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review of Cell and Developmental Biology, 30, 255–289. https://doi.org/10.1146/annurev-cellbio-101512-122326.

    Article  CAS  PubMed  Google Scholar 

  2. Yanez-Mo M, Siljander P, Andreu Z, Bedina A et al. (2015) Biological properties of extracellular vesicles and their physiological functions. Journal of Extracell Vesicles 4: 27066 – doi:https://doi.org/10.3402/jev.v4.27066.

  3. Barile, L., & Vassalli, G. (2017). Exosomes: therapy delivery tools and biomarkers of diseases. Pharmacology & Therapeutics, 174, 63–78.

    CAS  Google Scholar 

  4. Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. The Journal of Cell Biology, 200(4), 373–383. https://doi.org/10.1083/jcb.201211138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Poe, A., & Knowlton, A. (2017). Exosomes as agents of change in the cardiovascular system. Journal of Molecular and Cellular Cardiology, 111, 40–50. https://doi.org/10.1016/j.yjmcc.2017.08.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Record, M., Subra, C., Silvente-Poirot, S., & Poirot, M. (2011). Exosomes as intercellular signalosomes and pharmacological effectors. Biochemical Pharmacology, 81, 1171–1182.

    CAS  PubMed  Google Scholar 

  7. Malik, Z., Kott, K., Poe, A., Kuo, T., Chen, L., Ferrara, K., & Knowlton, A. (2013). Cardiac myocyte exosomes: stability, HSP60, and proteomics. American Journal of Physiology. Heart and Circulatory Physiology, 304, H954–H965. https://doi.org/10.1152/ajpheart.00835.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Caby, M., Lankar, D., Vincendeau-Scherrer, C., Raposo, G., & Bonnerot, C. (2005). Exosomal-like vesicles are present in human blood plasma. International Immunology, 17, 879–887. https://doi.org/10.1093/intimm/dxh267.

    Article  CAS  PubMed  Google Scholar 

  9. Keller, S., Ridinger, J., Rupp, A., Janssen, J., & Altevogt, P. (2011). Body fluid derived exosomes as a novel template for clinical diagnostics. Journal of Translational Medicine, 9, 86–95. https://doi.org/10.1186/1479-5876-9-86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sluijter, J., Verhage, V., Deddens, J., van den Akker, F., & Doevendans, P. (2014). Microvesicles and exosomes for intracardiac communication. Cardiovascular Research, 102, 302–311.

    CAS  PubMed  Google Scholar 

  11. Sahoo, S., & Losordo, D. W. (2014). Exosomes and cardiac repair after myocardial infarction. Circulation Research, 114, 333–344.

    CAS  PubMed  Google Scholar 

  12. Pironti, G., Strachan, R. T., Abraham, D., Mon-Wei, Y. U. S., Chen, M., Chen, W., Hanada, K., Mao, L., Watson, L. J., & Rockman, H. A. (2015). Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circ., 24, 2120–2130.

    Google Scholar 

  13. Kowal, J., Tkach, M., & Théry, C. (2014). Biogenesis and secretion of exosomes. Current Opinion in Cell Biology, 29, 116–125. https://doi.org/10.1016/j.ceb.2014.05.004.

    Article  CAS  PubMed  Google Scholar 

  14. Hanson, P. I., & Cashikar, A. (2012). Multivesicular body morphogenesis. Annual Review of Cell and Developmental Biology, 28, 337–362.

    CAS  PubMed  Google Scholar 

  15. Villarroya-Beltri, C., Baixauli, F., Gutierrez-Vazquez, C., Sanchez-Madrid, F., & Mittelbrunn, M. (2014). Sorting it out: regulation of exosome loading. Seminars in Cancer Biology, 28, 3–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Colombo, M., Moita, C., van Niel, G., Kowal, J., Vigneron, J., Benaroch, P., Manel, N., Moita, L. F., Thery, C., & Raposo, G. (2013). Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. Journal of Cell Science, 126(24), 5553–5565.

    CAS  PubMed  Google Scholar 

  17. Henne, W., Buchkovich, N., & Emr, S. (2011). The ESCRT pathway. Developmental Cell, 21(1), 77–91.

    CAS  PubMed  Google Scholar 

  18. Raiborg, C., & Stenmark, H. (2009). The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 458(7237), 445–452. https://doi.org/10.1038/nature07961.

    Article  CAS  PubMed  Google Scholar 

  19. Hurley, J., Boura, E., Carlson, L., & Różycki. (2010). Membrane budding. Cell., 143(6), 875–887. https://doi.org/10.1016/j.cell.2010.11.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stoorvogel, W., Kleijmeer, M., Geuze, H., & Raposo, G. (2002). The biogenesis and functions of exosomes. Traffic, 3, 321–330.

    CAS  PubMed  Google Scholar 

  21. Stoorvogel, W. (2015). Resolving sorting mechanisms into exosomes. Cell Research, 25, 531–532.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kowal, J., Tkach, M., & Thery, C. (2014). Biogenesis and secretion of exosomes. Current Opinion in Cell Biology, 29, 116–125.

    CAS  PubMed  Google Scholar 

  23. Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Brugger, B., & Trajkovic, K. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 319(5867), 1244–1247. https://doi.org/10.1126/science.1153124.

    Article  CAS  PubMed  Google Scholar 

  24. Maas, S., Breakefeld, X., & Weaver, A. (2017). Extracellular vesicles: unique intercellular delivery vehicles. Trends in Cell Biology, 27(3), 172–188. https://doi.org/10.1016/j.tcb.2016.11.003.

    Article  CAS  PubMed  Google Scholar 

  25. Hsu, C., Morohashi, Y., Yoshimura, S., Manrique-Hoyos, N., Jung, S., Lauterbach, M. A., Bakhti, M., Gronborg, M., Mobius, W., Rhee, J., Barr, F. A., & Simons, M. (2010). Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. The Journal of Cell Biology, 189(2), 223–232.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Seabra, M. C., Mules, E. H., & Hume, A. N. (2002). Rab GTPases, intracellular traffic and disease. Trends in Molecular Medicine, 8, 23–30.

    CAS  PubMed  Google Scholar 

  27. Savina, A., Vidal, M., & Colombo, M. (2002). The exosome pathway in K562 cells is regulated by Rab11. Journal of Cell Science, 115(Pt 12), 2505–2515.

    CAS  PubMed  Google Scholar 

  28. Pfeffer, S. (2010). Two Rabs for exosome release. Nature Cell Biology, 12, 3–4. https://doi.org/10.1038/ncb0110-3.

    Article  CAS  PubMed  Google Scholar 

  29. Ostrowski, M., Carmo, N., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C. F., Schauer, K., Hume, A., Freitas, R., Goud, B., Benaroch, P., Hacohen, N., Fukuda, M., Desnos, C., Seabra, M., Darchen, F., Amigorena, S., Moita, L., & Thery, C. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature Cell Biology, 12(1), 19–30 sup pp 1–13.

    CAS  PubMed  Google Scholar 

  30. Ali, B., & Seabra, M. (2005). Targeting of Rab GTPases to cellular membranes. Biochemical Society Transactions, 33, 652–656.

    CAS  PubMed  Google Scholar 

  31. Jahn, R., & Scheller, R. H. (2006). SNAREs--engines for membrane fusion. Nature Reviews. Molecular Cell Biology, 7(9), 631–643.

    CAS  PubMed  Google Scholar 

  32. Fader, C., Sanchez, D., Mestre, M., & Colombo, M. (2009). v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Et Biophys Acta-Mol Cell Res., 1793(12), 1901–1916.

    CAS  Google Scholar 

  33. French, K., Antonyak, M., & Cerione, R. (2017). Extracellular vesicle docking at the cellular port: extracellular vesicle binding and uptake. Seminars in Cell & Developmental Biology, 67, 48–55. https://doi.org/10.1016/j.semcdb.2017.01.002.

    Article  CAS  Google Scholar 

  34. Qui, G., Zheng, G., Ge, M., Wang, J., Huang, R., Shu, Q., & Xu, J. (2018). Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Research & Therapy, 9, 320–329. https://doi.org/10.1186/s13287-018-1069.

    Article  Google Scholar 

  35. Rana, S., Yue, S., Stadel, D., & Zöller, M. (2012). Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. The International Journal of Biochemistry & Cell Biology, 44(9), 1574–1584.

    CAS  Google Scholar 

  36. Yoshioka, Y., Konishi, Y., Kosaka, N., Nobuyoshi, K., Takeshi, K., Takashi, K., & Takahiro, O. (2013). Comparative marker analysis of extracellular vesicles in different human cancer types. J Extracell Vesicles., 2, 10.3402. https://doi.org/10.3402/jev.v2i0.20424.

    Article  CAS  Google Scholar 

  37. Gurunathan, S., Kang, M.-H., Jeyaraj, M., Qasim, M., & Kim, J.-H. (2019). Review of the isolation, characterization, biological function and multifarious therapeutic approaches of exosomes. Cells, 8, 307–343. https://doi.org/10.3390/cells804030737.

    Article  CAS  PubMed Central  Google Scholar 

  38. Takov, K., Yellon, D., & Davidson, S. (2017). Confounding factors in vesicle uptake studies using fluorescent lipophilic membrane dyes. J Extracell Vesicles., 6, 1388731. https://doi.org/10.1080/20013078.2017.1388731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zeringer, E., Barta, T., Li, M., & Vlassov, A. (2015). Strategies for isolation of exosomes. Cold Spring Harbor Protocols. https://doi.org/10.1101/pdb.top074476.

  40. Wu, M., Ouyang, Y., Wang, Z. R., Huang, P.-H., Chen, C., Li, H., Li, P., Quinn, D., Dao, M., Suresh, S., Sadovsky, Y., & Huang, T. (2017). Acoustofluidic exosome isolation from whole blood. Pro Nat Acad Sci, 114(40), 10584–10589. https://doi.org/10.1073/pnas.1709210114.

    Article  CAS  Google Scholar 

  41. Gennebäck, N., Hellman, U., Malm, L., Larsson, G., Ronquist, G., Waldenström, A., & Mörner, S. (2013). Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes. J Extracell Vesicles, 2. https://doi.org/10.3402/jev.v2i0.20167.

  42. Szatanek, R., Baj-Krzyworzeka, M., Zimoch, J., Lekka, M., Siedlar, M., & Baran, J. (2017). The methods of choice for extracellular vesicles (EVs) characterization. International Journal of Molecular Sciences, 18, 1153.

    PubMed Central  Google Scholar 

  43. Erdbrügger, U., & Lannigan, J. (2015). Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry. Part A, 89, 123–134.

  44. Hessvik, N., Liorente, A. (2018). Current knowledge on exosome biogenesis and release. Cell and Moll Life Sci, 75(2), 193–208. https://doi.org/10.1007/s00018-017-2595-9.

    Article  CAS  Google Scholar 

  45. Li, P., Kaslan, M., Lee, S. H., Yao, J., & Gao, Z. (2017). (2017) Progress in exosome isolation techniques. Theranost., 7(3), 789–804. https://doi.org/10.7150/thno.18133.

    Article  CAS  Google Scholar 

  46. Thery, C., Witwer, K., Aikawa, E., et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7(1), 1535750. https://doi.org/10.1080/20013078.2018.1535750.

  47. Garikipati, V., Shoja-Taheri, F., Davis, M., & Kishore, R. (2018). Extracellular vesicles and the application of system biology and computational modeling in cardiac repair. Circulation Research, 123, 188–204. https://doi.org/10.1161/CIRCRESAHA.117.311215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Waldenstrom, A., Genneback, N., Hellman, U., & Ronquist, G. (2012). Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One, 7, e34653.

  49. Malik, Z., Kott, K., Poe, A., Kuo, T., Chen, L., Ferrara, K., & Knowlton, A. (2013). Cardiac myocyte exosomes: stability, HSP60, and proteomics. American Journal of Physiology. Heart and Circulatory Physiology, 304(7), H954–H965. https://doi.org/10.1152/ajpheart.00835.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ribeiro, M., Zhu, H., Millard, R., & Fan, G. (2013). Exosomes function in pro- and anti-angiogenesis. Curr. Angiogenes, 2, 54–59. https://doi.org/10.2174/22115528113020020001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Stastna, M., Chimenti, I., Marban, E., & Van Eyk, J. (2010). Identification and functionality of proteomes secreted by rat cardiac stem cells and neonatal cardiomyocytes. Proteom., 10, 245–253.

    CAS  Google Scholar 

  52. Bei Y, Chen T, Banciu D, Cretoiu D, Xiao J. (2017) Circulating exosomes in cardiovascular diseases. In: Xiao J., Cretoiu S. (eds) Exosomes in Cardiovascular Diseases. Advan Exper Med and Bio, Springer, Singapore, vol 998.

  53. Garcia, N., Moncay-Arlandi, J., Sepulveda, P., & Diez-Juan, A. (2016). Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes. Cardiovascular Research, 109, 397–408. https://doi.org/10.1093/cvr/cvv260.

    Article  CAS  PubMed  Google Scholar 

  54. Garcia, N., Ontoria-Oviedo, I., González-King, H., Diez-Juan, A., & Sepúlveda, P. (2015). Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS One, 10, e0138849. https://doi.org/10.1371/journal.pone.0138849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gupta, S., & Knowlton, A. (2007). HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. American Journal of Physiology. Heart and Circulatory Physiology, 292, H3052–H3056.

    CAS  PubMed  Google Scholar 

  56. Yu, X., Deng, L., Wang, D., Li, N., Chen, X., Cheng, X., Yuan, J., Gao, X., Liao, M., Wang, M., & Liao, Y. (2012). Mechanism of TNF-α autocrine effects in hypoxic cardiomyocytes: initiated by hypoxia inducible factor 1α, presented by exosomes. J Mol Cell Cardiol, 53, 848–857. https://doi.org/10.1016/j.yjmcc.2012.10.002.

    Article  CAS  PubMed  Google Scholar 

  57. Wang, X., Gu, H., Huang, W., Peng, J., Li, Y., Yang, L., Qin, D., Essandoh, K., Wang, Y., Peng, T., & Fan, G. (2016). Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice. Diabet., 65(10), 3111–3128.

    CAS  Google Scholar 

  58. Louapre, P., Grongnet, J., Tanguay, R., & David, J. (2005). Effects of hypoxia on stress proteins in the piglet heart at birth. Cell Stress & Chaperones, 10, 17–23.

    CAS  Google Scholar 

  59. Yu, H., & Wang, Z. (2019). Cardiomyocyte-derived exosomes: biological functions and potential therapeutic implications. Frontiers in Physiology, 10, 1049–1058. https://doi.org/10.3389/fphys.2019.01049.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Wang, X., Gu, H., Huang, W., Peng, J., Li, Y., Yang, L., Qin, D., Essandoh, K., Wang, Y., Peng, T., & Fan, G. (2016). Hsp20-mediated activation of exosome biogenesis in cardiomyocytes improves cardiac function and angiogenesis in diabetic mice. Diabetes, 65(10), 3111–3128. https://doi.org/10.2337/db15-1563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang, X., Wang, X., Zhu, H., Kranias, E., Tang, Y., Peng, T., Chang, J., & G-Cl, F. (2012). Hsp20 functions as a novel cardiokine in promoting angiogenesis via activation of VEGFR2. PLoS One, 7, e32765. https://doi.org/10.1371/journal.pone.0032765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Feng, Y., Huang, W., Meng, W., Jegga, A., Wang, Y., Cai, W., Kim, H., Pasha, Z., Wen, Z., Rao, F., Modi, R., Yu, X., & Ashraf, M. (2014). Heat shock improves Sca-1+ stem cell survival and directs ischemic cardiomyocytes toward a prosurvival phenotype via exosomal transfer: a critical role for HSF1/miR-34a/HSP70 pathway. Stem Cells, 32, 462–472. https://doi.org/10.1002/stem.1571.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Yu, X., Deng, L., Wang, D., Li, N., Chen, X., Cheng, X., Yuan, J., Gao, X., Liao, M., Wang, M., & Liao, Y. (2012). Mechanism of TNF-a autocrine effects in hypoxic cardiomyocytes: initiated by hypoxia inducible factor 1a, presented by exosomes. Journal of Molecular and Cellular Cardiology, 53, 848–857. https://doi.org/10.1016/j.yjmcc.2012.10.002.

    Article  CAS  PubMed  Google Scholar 

  64. Datta, R., Bansal, T., Rana, S., Datta, K., Datta Chaudhur, R., Chawla-Sarkar, M., & Sarar, S. (2017). Myocyte-derived Hsp90 modulates collagen upregulation via biphasic activation of STAT-3 in fibroblasts during cardiac hypertrophy. Molecular and Cellular Biology, 37, e00611–e00616. https://doi.org/10.1128/MCB.00611-16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yates, L., Norbury, C., & Gilbert, R. (2013). The long and short of MicroRNA. Cell, 153(3), 516–519. https://doi.org/10.1016/j.cell.2013.04.003. 

  66. Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 19, 92–105.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Bollini, S., Smits, A., Balbi, C., Lazzarini, E., & Amer, P. (2018). Triggering endogenous cardiac repair and regeneration via extracellular vesicle-mediated communication. Frontiers in Physiology, 9, 1497. https://doi.org/10.3389/fphys.2018.01497.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Deng, F., Xu, X., & Chen, Y. (2014). The role of miR-1 in the heart: from cardiac morphogenesis to physiological function. Human Genet Embryol., 4, 1. https://doi.org/10.4172/2161-0436.1000119.

    Article  Google Scholar 

  69. Xu, C., Lu, Y., Pan, Z., Chu, W., Luo, X., Lin, H., Xiao, J., Shan, H., Wang, Z., & Yang, B. (2007). The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. Journal of Cell Science, 120, 3045–3052.

    CAS  PubMed  Google Scholar 

  70. Castoldi, G., di Gioia, C., Bombardi, C., Catalucc, D., Corradi, B., Gualazzi, M., Leopizzi, M., Mancini, M., Zerbini, G., Condorell, G., & Stella, A. (2012). MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension. Journal of Cellular Physiology, 227, 850–856.

    CAS  PubMed  Google Scholar 

  71. Kozakowska, M., Ciesla, M., Stefanska, A., Skrzypek, K., Was, H., Jazwa, A., Grochot-Przeczek, A., Kotlinowski, J., Szymula, A., Bartelik, A., Mazan, M., Yagensky, O., Florczyk, U., Lemke, K., Zebzda, A., Dyduch, G., Nowak, W., Szade, K., Stepniewski, J., Majka, M., Derlacz, R., Loboda, A., Dulak, J., & Jozkowicz, A. (2012). Heme oxygenase-1 inhibits myoblast differentiation by targeting myomirs. Antioxidants & Redox Signaling, 16(2), 113–127. https://doi.org/10.1089/ars.2011.3964.

    Article  CAS  Google Scholar 

  72. Li, X., Wang, J., Jia, Z., Cui, Q., Zhang, C., Wang, W., Chen, P., Ma, K., & Zhou, C. (2013). MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac differentiation via Sox6 and cyclin D1. PLoS One, 8(9), e74504. https://doi.org/10.1371/journal.pone.0074504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Izarra, A., Moscoso, I., Levent, E., Cañón, S., Cerrada, I., Díez-Juan, A., Blanca, V., Núñez-Gil, I., Valiente, I., Ruíz-Sauri, A., Sepulveda, P., Tiburcy, M., Zimmermann, W., & Berna, A. (2014). miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Reports, 3, 1029–1042.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Wang, J., Jia, Z., Zhang, C., Sun, M., Wang, W., Chen, P., Ma, K., Zhang, Y., Li, X., & Zhou, C. (2014). miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects on Pdcd4 and Pacs2. RNA Biology, 11, 339–350.

    PubMed  PubMed Central  Google Scholar 

  75. Li, S., Xiao, F., Shan, P., Su, L., Chen, D., Ding, J., & Wang, Q. (2015). Overexpression of microRNA-133a inhibits ischemia-reperfusion-induced cardiomyocyte apoptosis by targeting DAPK2. Journal of Human Genetics, 60(11), 709–716. https://doi.org/10.1038/jhg.2015.96.

    Article  CAS  PubMed  Google Scholar 

  76. Matsui, Y., Takagi, H., Qu, X., Abdellatif, M., Sakoda, H., Asano, T., Levine, B., & Sadoshima, J. (2007). Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circulation Research, 100(6), 914–922.

    CAS  PubMed  Google Scholar 

  77. Yang, J., Yu, X., Xue, F., Li, Y., Liu, W., & Zhang, S. (2018). Exosomes derived from cardiomyocytes promote cardiac fibrosis via myocyte-fibroblast crosstalk. American Journal of Translational Research, 10, 4350–4366.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Vanhaverbeke, M., Gal, D., & Holvoet, P. (2017). Functional role of cardiovascular exosomes in myocardial injury and atherosclerosis. In J. Xiao & S. Cretoiu (Eds.), Exosomes in cardiovascular diseases. Advances in Experimental Medicine and Biology (Vol. 998, pp. 45–58). Singapore: Springer.

    Google Scholar 

  79. Kuo, H., Hsieh, C., Wang, S., Chang, C., Hung, C., Kuo, L., Liu, Y.-R., Li, C.-Y., & Liu, P.-L. (2019). Simvastatin attenuates cardiac fibrosis via regulation of cardiomyocyte derived exosome secretion. Journal of Clinical Medicine, 8, E794. https://doi.org/10.3390/jcm8060794.

    Article  CAS  PubMed  Google Scholar 

  80. Wang, X., Huang, W., Liu, G., Cai, W., Millard, R. W., Wang, Y., Chang, J., Peng, T., & Fan, G. (2014). Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. Journal of Molecular and Cellular Cardiology, 74, 139–150. https://doi.org/10.1016/j.yjmcc.2014.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Davidson, S., Riquelme, J., Takov, K., Vicencio, J., Boi-Doku, C., Khoo, V., Doreth, C., Radenkovic, D., Lavandero, S., & Yellon, D. (2018). Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non-diabetic exosomes in vitro. Journal of Cellular and Molecular Medicine, 22, 141–151.

    CAS  PubMed  Google Scholar 

  82. van Balkom, B., de Jong, O., Smits, M., Brummelman, J., den Ouden, K., de Bree, P., van Eijndhoven, M., Pegtel, D., Stoorvogel, W., Würdinger, T., & Verhaar, M. (2013). Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood., 121(3997–4006), S1–S15. https://doi.org/10.1182/blood-2013-02-478925.

    Article  CAS  Google Scholar 

  83. Njock, M., Cheng, H., Dang, L., Nazari-Jahantigh, M., Lau, A., Boudreau, E., Roufaiel, M., Cybulsky, M. I., Schober, A., & Fish, J. (2015). Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing antiinflammatory microRNAs. Blood., 125(20), 3202–3212.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Vasa-Nicoteraa, M., Chena, H., Tuccia, P., Yanga, A., Saintignyc, G., Menghinid, R., Mahec, C., Agostinia, M., Knight, R., Melino, G., & Federic, M. (2011). miR-146a is modulated in human endothelial cell with aging. Athero., 217(2), 326–330. https://doi.org/10.1016/j.atherosclerosis.2011.03.034.

  85. Lyu, L., Wang, H., Li, B., Qin, Q., Qi, L., Nagarkatti, M., Nagarkatti, P., Janicki, J., Wang, X., & Cui, T. (2015). A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes. Journal of Molecular and Cellular Cardiology, 89, 268–279. https://doi.org/10.1016/j.yjmcc.2015.10.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A., Tsuchihashi, T., McManus, M. T., Schwartz, R. J., & Srivastava, D. (2007). Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell, 129, 303–317. https://doi.org/10.1016/j.cell.2007.03.030.

  87. Tian, C., Gao, L., Zimmerman, M., & Zucker, I. (2018). Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure. American Journal of Physiology. Heart and Circulatory Physiology, 314, H928–H939. https://doi.org/10.1152/ajpheart.00602.2017.

  88. Yang, Y., Li, Y., Chen, X., Cheng, X., Liao, Y., & Yu, X. (2016). Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia. Journal of Molecular Medicine, 94, 711–724. https://doi.org/10.1007/s00109-016-1387-287.

    Article  CAS  PubMed  Google Scholar 

  89. Oliveira-Carvalho, V., da Silva, M., Guimarães, G., Bacal, F., & Bocchi, E. (2013). MicroRNAs: new players in heart failure. Molecular Biology Reports, 40(3), 2663–2670. https://doi.org/10.1007/s11033-012-2352-y.

    Article  CAS  PubMed  Google Scholar 

  90. He, B., Xiao, J., Ren, A., Zhang, Y.-F., Zhang, H., Chen, M., Xie, B., Gao, X.-G., & Wang, Y.-W. (2011). Role of miR-1 and miR-133a in myocardial ischemic postconditioning. Journal of Biomedical Science, 18, 22. https://doi.org/10.1186/1423-0127-18-22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Puthanveetila, P., Benga, B., Matkovichb, S., Dorn, G., & Chakrabarti, S. (2014). Cardiac miR-133a overexpression preventsearly cardiac fibrosis in diabetes. Journal of Cellular and Molecular Medicine, 18(3), 415–421.

    Google Scholar 

  92. Oliveira-Carvalho, V., Carvalho, V., & Bocchi, E. (2013). (2013) The emerging role of miR-208a in the heart. DNA and Cell Biology, 32(1), 8–12. https://doi.org/10.1089/dna.2012.1787.

    Article  CAS  PubMed  Google Scholar 

  93. Nie, X., Fan, J., Li, H., Yin, Z., Zhao, Y., Dai, B., Dong, N., Chen, C., & Wang, D. W. (2018). MiR-217 promotes cardiac hypertrophy and dysfunction by targeting PTEN. Molecular Therapy--Nucleic Acids, 12, 254–266.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Fish, J., Santoro, M., Morton, S., Yu, S., Yeh, R., Wythe, J., Ivey, K., Bruneau, B., Stainier, D., & Srivastava, D. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Developmental Cell, 5(2), 272–284.

    Google Scholar 

  95. Wang, S., Aurora, A., Johnson, B., Qi, X., McAnally, J., Hill, J., Richardson, J., Bassel-Duby, R., & Olson, E. (2008). The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Developmental Cell, 15(2), 261–271.

    PubMed  PubMed Central  Google Scholar 

  96. Chen, Y., & Gorski, D. (2008). Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood, 111(3), 1217–1226.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Halkein, J., Tabruyn, S., Ricke-Hoch, M., Haghikia, A., Nguyen, N., Scherr, M., Castermans, K., Malvaux, L., Lambert, V., Thiry, M., Sliwa, K., Noel, A., Martial, J., Hilfiker-Kleiner, D., & Struman, I. (2013). MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. The Journal of Clinical Investigation, 123, 2143–2154. https://doi.org/10.1172/JCI64365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Teng, X., Chen, L., Chen, W., Yang, J., Yang, Z., & Shen, Z. (2015). Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cellular Physiology and Biochemistry, 37, 2415–2424.

    CAS  PubMed  Google Scholar 

  99. Yu, B., Kim, H., Gong, M., Wang, J., Millard, R., Wang, Y., Ashraf, M., & Xu, M. (2015). Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. International Journal of Cardiology, 182, 349–360.

    PubMed  Google Scholar 

  100. Vrijsen, K., Maring, J., Chamuleau, S., Verhage, V., Mol, E., Deddens, J., Metz, C., Lodder, K., van Eeuwijk, E., van Dommelen, S., Doevendans, P., Smits, A., Goumans, M., & Sluijter, J. (2016). Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Advanced Healthcare Materials, 5, 2555–2565.

    CAS  PubMed  Google Scholar 

  101. Lai, R., Tan, S., Teh, B., Sze, S., Arslan, F., de Kleijn, D., Choo, A., & Lim, S. (92012). Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome. Int J Proteom, 2012, 971907. https://doi.org/10.1155/2012/971907.

  102. Chen T, Lai R, Lee M, Choo A, Lee C, Lim S. (2010) Mesenchymal stem cell secretes microparticles enriched in premicroRNAs. Nuc Acids Res.38:215–224.

  103. Chen, L., Wang, Y., Pan, Y., Zhang, L., Shen, C., Qin, G., Ashraf, M., Weintraub, N., Ma, G., & Tang, Y. (2013). Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochemical and Biophysical Research Communications, 431, 566–571. https://doi.org/10.1016/j.bbrc.2013.01.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Barile, L., Lionetti, V., Cervio, E., Matteucci, M., Gherghiceanu, M., Popescu, L. M., Torre, T., Siclari, F., Moccetti, T., & Vassalli, G. (2014). Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovascular Research, 103(4), 530–541. https://doi.org/10.1093/cvr/cvu167.

    Article  CAS  PubMed  Google Scholar 

  105. Ibrahim, A., Cheng, K., & Marb#an E. (2014). Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports, 5, 606–619.

    Google Scholar 

  106. Chen, L., Wang, Y., Pan, Y., Zhang, L., Shen, C., Qin, G., Ashraf, M., Weintraub, N., Ma, G., & Tang, Y. (2013). Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochemical and Biophysical Research Communications, 431(3), 566–571.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Xiao, J., Pan, Y., Li, X., Yang, X., Feng, Y., Tan, H., Jiang, L., Feng, J., & Yu, X. (2016). Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death & Disease, 7, e2277.

    CAS  Google Scholar 

  108. Agarwal, U., George, A., Bhutani, S., Ghosh-Choudhary, S., Maxwell, J., Brown, M., Mehta, Y., Platt, M., Liang, Y., Sahoo, S., & Davis, M. (2017). Experimental, systems, and computational approaches to understanding the MicroRNA-mediated reparative potential of cardiac progenitor cell-derived exosomes from pediatric patients. Circulation Research, 120(4), 701–712.

    CAS  PubMed  Google Scholar 

  109. Sharma, S., Mishra, R., Bigham, G. E., Wehman, B., Khan, M. M., Xu, H., Saha, P., Goo, Y., Datla, S., Chen, L., Tulapurkar, M., Taylor, B., Yang, P., Karathanasis, S., Goodlett, D., & Kaushal, S. (2017). A deep proteome analysis identifies the complete secretome as the functional unit of human cardiac progenitor cells. Circulation Research, 120(5), 816–834.

    CAS  PubMed  Google Scholar 

  110. Lin, C., Li, S., Deng, S., Fu, X., Qin, A., & Yu, X. (2019). The role of stem cell-derived exosomes in repairing myocardial injury. Sheng Li Xue Bao, 71(2), 205–215. https://doi.org/10.13294/j.aps.2019.0010.

    Article  PubMed  Google Scholar 

  111. Duan, P., Tan, J., Miao, Y., & Zhang, Q. (2019). Potential role of exosomes in the pathophysiology, diagnosis, and treatment of hypoxic diseases. American Journal of Translational Research, 11(3), 1184–1201.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Moghaddama, A., Afsharia, J., Esmaeilib, S.-A., Saburid, E., Joneidif, Z., & Momtazi-Borojenig, A. (2019). Cardioprotective microRNAs: lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease. Athero., 285, 1–9.

    Google Scholar 

  113. Mol, E., Goumans, M., & Sluijter, J. (2017). Cardiac progenitor-cell derived exosomes as cell-free therapeutic for cardiac repair. Exosomes in cardiovascular diseases: biomarkers, pathological and therapeutic effects. Advances in Experimental Medicine and Biology, 98, 207–219.

    Google Scholar 

  114. Srivastava, D., & Ivey, K. (2006). Potential of stem-cell-based therapies for heart disease. Nature, 441, 1097–1099. https://doi.org/10.1038/nature04961.

    Article  CAS  PubMed  Google Scholar 

  115. Khan, M., Nickoloff, E., Abramova, T., Johnson, J., Verma, S., Krishnamurthy, P., Mackie, A., Vaughan, E., Garikipati, V., Benedict, C., Ramirez, V., Lambers, E., Ito, A., Gao, E., Misener, S., Luongo, T., Elrod, J., Qin, G., Houser, S., Koch, W., & Kishore, R. (2015). Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circulation Research, 117(1), 52–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Xiao, J., Pan, Y., Li, X., Yang, X., Feng, Y., Tan, H., Jiang, L., Feng, J., & Yu, X. Y. (2016). Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death & Disease, 7(6), e2277.

    CAS  Google Scholar 

  117. Gray, W., French, K., Ghosh-Choudhary, S., Maxwell, J., Brown, M., Platt, M., Searles, C., & Davis, M. (2015). Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circulation Research, 116(2), 255–263. https://doi.org/10.1161/CIRCRESAHA.116.304360.

    Article  CAS  PubMed  Google Scholar 

  118. Luthera, K., Haara, L., McGuinessa, M., Wanga, Y., Lynch, T., Phana, A., Songa, Y., Shenb, Z., Gardnerb, G., Kuffeia, G., Rena Xm Zilloxa, M., & Jonesa, W. (2018). Exosomal miR-21a-5p mediates cardioprotection by mesenchymal stem cell. Journal of Molecular and Cellular Cardiology, 119, 125–137.

    Google Scholar 

  119. Feng Y, Huang W, Wani M, Yu X, Ashraf M. (2014) Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22 PLoS One 9(2): e88685.

  120. Ottaviani, L., Sansonetti, M., & da Costa Martins, P. A. (2018). Myocardial cell-to-cell communication via microRNAs. Noncoding RNA Res., 3(3), 144–153. https://doi.org/10.1016/j.ncrna.2018.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang, B., Komers, R., Carew, R., Winbanks, C., Xu, B., Herman-Edelstein, M., Koh, P., Thomas, M., Jandeleit-Dahm, K., Gregorevic, P., Cooper, M., & Kantharidis, P. (2012). Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol., 23(2), 252–265. https://doi.org/10.1681/ASN.201101005521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Wang, K., Jiang, Z., Webster, K. A., Chen, J. H., Hu, H. X., Zhou, Y., Zhao, J., Wang, L. H., Wang, Y. C., Zhong, Z. W., Ni, C., Li, Q. J., Xiang, C., Zhang, L., Wu, R., Zhu, W., Yu, H., Hu, X., & Wang, J. (2017). Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal microRNA-21. Stem Cells Translational Medicine, 6(1), 209–222.

    CAS  PubMed  Google Scholar 

  123. Park, H., Park, H., Mun, D., Kang, J., Kim, H., Kim, M., Cui, S., Lee, S., & Joung, B. (2018). Extracellular vesicles derived from hypoxic human mesenchymal stem cells attenuate gsk3β expression via mirna-26a in an ischemia-reperfusion injury model. Yonsei Medical Journal, 59, 736–745. https://doi.org/10.3349/ymj.2018.59.6.736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Wang, N., Chen, C., Yang, D., Liao, Q., Luo, H., Wang, X., Zhou, F., Yang, X., Yang, J., Zeng, C., & Wang, W. (2017). Mesenchymal stem cells-derived extracellular vesicles, via miR-210, improve infarcted cardiac function by promotion of angiogenesis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1863(8), 2085–2092.

    CAS  PubMed  Google Scholar 

  125. Xiao, C., Wang, K., Xu, Y., Hu, H., Zhang, N., Wang, Y., Zhong, Z., Zhao, J., Li, Q., Zhu, D., Ke, C., Zhong, S., Wu, X., Yu, H., Zhu, W., Chen, J., Zhang, J., Wang, J., & Hu, X. (2018). Transplanted mesenchymal stem cells reduce autophagic flux in infarcted hearts via the exosomal transfer of miR-125b. Circulation Research, 123(5), 564–578. https://doi.org/10.1161/CIRCRESAHA.118.312758.

    Article  CAS  PubMed  Google Scholar 

  126. Namazi, H., Mohit, E., Namazi, I., Rajabi, S., Samadian, A., Hajizadeh-Saffar, E., Aghdami, N., & Baharvand, H. (2018). Exosomes secreted by hypoxic cardiosphere-derived cells enhance tube formation and increase pro-angiogenic miRNA. Journal of Cellular Biochemistry, 119(5), 4150–4160.

    CAS  PubMed  Google Scholar 

  127. de Couto, G., Gallet, R., Cambier, L., Jaghatspanyan, E., Makkar, N., Dawkins, J., Berman, B., & Marban, E. (2017). Exosomal MicroRNA transfer into macrophages mediates cellular postconditioning. Circ., 136(2), 200–214.

    Google Scholar 

  128. Li J, Wan W, Chen T, Tong S, Jiang X, Liu W. (2019) miR-451 silencing inhibited doxorubicin exposure-induced cardiotoxicity in mice. BioMed Research International Article ID 1528278, 11 pages. doi:https://doi.org/10.1155/2019/1528278.

  129. Shi, B., Wang, Y., Zhao, R., Long, X., Deng, W., & Wang, Z. (2018). Bone marrow mesenchymal stem cell-derived exosomal miR-21 protects C-kit(+) cardiac stem cells from oxidative injury through the PTEN/PI3K/Akt axis. PLoS One, 13(2), e0191616.

    PubMed  PubMed Central  Google Scholar 

  130. Luo, Q., Guo, D., Liu, G., Chen, G., Hang, M., & Jin, M. (2017). Overexpressing ADscs are therapeutic in relieving acute myocardial ischaemic injury. Cellular Physiology and Biochemistry, 44, 2105–2116. https://doi.org/10.1159/000485949.

    Article  CAS  PubMed  Google Scholar 

  131. Kwak, J., Choi, S., Oh, W., Yang, Y., Jeon, H., & Jeon, E. (2018). Cobalt chloride enhances the anti-inflammatory potency of human umbilical cord blood-derived mesenchymal stem cells through the erk-hif-1α-microrna-146a-mediated signaling pathway. Stem Cells Internat, 2018:Article ID 4978763. https://doi.org/10.1155/2018/4978763.29.

  132. Emanueli, C., Shearn, A., Angelini, G., & Sahoo, S. (2015). Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascular Pharmacology, 71, 24–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Kuwabara, Y., Ono, K., Horie, T., Nishi, H., Nagao, K., Kinoshita, M., Watanabe, S., Baba, O., Kojima, Y., Shizuta, S., Imai, M., Tamura, T., Kita, T., & Kimura, T. (2011). Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circulation. Cardiovascular Genetics, 4, 446–454.

    CAS  PubMed  Google Scholar 

  134. Cheng, Y., Wang, X., Yang, J., Duan, X., Yao, Y., Shi, X., Chen, Z., Fan, Z., Liu, X., Qin, S., Tang, X., & Zhang, C. (2012). A translational study of urine miRNAs in acute myocardial infarction. Journal of Molecular and Cellular Cardiology, 53, 668–676.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. D’Alessandra, Y., Devanna, P., Limana, F., Straino, S., Di Carlo, A., Brambilla, P. G., Rubino, M., Carena, M. C., Spazzafumo, L., De Simone, M., Micheli, B., Biglioli, P., Achilli, F., Martelli, F., Maggiolini, S., Marenzi, G., Pompilio, G., & Capogrossi, M. C. (2010). Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. European Heart Journal, 31, 2765–2773.

    PubMed  PubMed Central  Google Scholar 

  136. Olivieri, F., Antonicelli, R., Lorenzi, M., D’Alessandra, Y., Lazzarini, R., Santini, G., Spazzafumo, L., Lisa, R., La, S., Galeazzi, R., Recchioni, R., Testa, R., Pompilio, G., Capogrossi, M., & Procopio, A. (2013). Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. International Journal of Cardiology, 167, 531–536.

    PubMed  Google Scholar 

  137. Wang, G. K., Zhu, J. Q., Zhang, J. T., Li, Q., Li, Y., He, J., Qin, Y. W., & Jing, Q. (2010). Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. European Heart Journal, 31, 659–666.

    PubMed  Google Scholar 

  138. Bi, S., Wang, C., Jin, Y., Lv, Z., Xing, X., & Lu, Q. (2015). Correlation between serum exosome derived miR-208a and acute coronary syndrome. International Journal of Clinical and Experimental Medicine, 8, 4275–4280.

    PubMed  PubMed Central  Google Scholar 

  139. Matsumoto, S., Sakata, Y., Suna, S., Nakatani, D., Usami, M., Hara, M., Kitamura, T., Hamasaki, T., Nanto, S., Kawahara, Y., & Komuro, I. (2013). Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circulation Research, 113(3), 322–326.

    CAS  PubMed  Google Scholar 

  140. Jakob, P., Doerries, C., Briand, S., Mocharla, P., Krankel, N., Besler, C., Mueller, M., Manes, C., Templin, C., Baltes, C., Rudin, M., Adams, H., Wolfrum, M., Noll, G., Ruschitzka, F., Luscher, T., & Landmesser, U. (2012). Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity. Circulation, 126(25), 2962–2975.

    CAS  PubMed  Google Scholar 

  141. Jansen, F., Yang, X., Proebsting, S., Hoelscher, M., Przybilla, D., Baumann, K., Schmitz, T., Dolf, A., Endl, E., Franklin, B., Sinning, J., Vasa-Nicotera, M., Nickenig, G., & Werner, N. (2014). MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. Journal of the American Heart Association, 3(6), e001249. https://doi.org/10.1161/JAHA.114.001249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Luo, H., Li, X., Li, T., Zhao, L., He, J., Zha, L., Qi, Q., & Yu, Z. (2019). microRNA-423-3p exosomes derived from cardiac fibroblasts mediates the cardioprotective effects of ischaemic post-conditioning. Cardiovascular Research, 115(7), 1189–1204. https://doi.org/10.1093/cvr/cvy231.

    Article  CAS  PubMed  Google Scholar 

  143. Cheng, M., Zhao, X., Wu, B., Mao, X., Yi, G., Zeng, Q., & Qin, G. (2014). Circulating exosomal miR-1a is markedly induced by myocardial infarction and downregulates CXCR4 expression in the bone marrow mononuclear cells. Circ., 130, A18383.

    Google Scholar 

  144. Yang, Y., Li, Y., Chen, X., Cheng, X., Liao, Y., & Yu, X. (2016). Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia. Journal of Molecular Medicine (Berlin, Germany), 94, 711–724.

    CAS  Google Scholar 

  145. Li, J., Gelber, R., Rutka, J., Sabah, N., Gladstone, R., Wei, C., Hu, P., Kharbanda, R., & Redington, A. (2014). MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Research in Cardiology, 109, 423. https://doi.org/10.1007/s00395-014-0423-z.

    Article  CAS  PubMed  Google Scholar 

  146. Aurora, A., Mahmoud, A., Luo, X., Johnson, B., van Rooij, E., Matsuzaki, S., Humphries, K., Hill, J., Bassel-Duby, R., Sadek, H., & Olson, E. (2012). MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death. The Journal of Clinical Investigation, 122(4), 1222–1232. https://doi.org/10.1172/JCI59327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Chaturvedi, P., Kalani, A., Medina, I., Familtseva, A., & Tyagi, S. (2015). Cardiosome-mediated regulation of MMP9 in diabetic heart: role of mir29b and mir455 in exercise. Journal of Cellular and Molecular Medicine, 19, 2153–2161.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Vicencio, J., Yellon, D., Sivaraman, V., Das, D., Boi-Doku, C., Arjun, S., Zheng, Y., Riquelme, J., Kearney, J., Sharma, V., Multhoff, G., Hall, A., & Davidson, S. (2015). Plasma exosomes protect the myocardium from ischemia-reperfusion injury. Journal of the American College of Cardiology, 65, 1525–1536. https://doi.org/10.1016/j.jacc.2015.02.026.

    Article  CAS  PubMed  Google Scholar 

  149. Zhang, X., Wang, X., Zhu, H., Kranias, E. G., Tang, Y., Peng, T., et al. (2012). Hsp20 functions as a novel cardiokine in promoting angiogenesis via activation of VEGFR2. PLoS One, 7, e32765. https://doi.org/10.1371/journal.pone.0032765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Zhang, C., Wu, J., Xu, X., Potter, B., & Gao, X. (2010). Direct relationship between levels of TNF-alpha expression and endothelial dysfunction in reperfusion injury. Basic Research in Cardiology, 105, 453–464.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Tian, J., Guo, X., Liu, X., Liu, L., Weng, Q., Dong, S., Knowlton, A., Yuan, W., & Lin, L. (2013). Extracellular HSP60 induces inflammation through activating and up-regulating TLRs in cardiomyocytes. Cardiovascular Research, 98, 391–401.

    CAS  PubMed  Google Scholar 

  152. Loyer, X., Zlatanova, I., Devue, C., Yin, M., Howangyin, K., Klaihmon Pzannis, K., Fleischmann, B., Hwang, D., Park, J., Lee, H., Menasche, P., Silvestre, J.-S., & Bourlanger, C. (2018). Intra-cardiac release of extracellular vesicles shapes inflammation following myocardial infarction. Circulation Research, 123, 100–106. https://doi.org/10.1161/CIRCRESAHA.117.311326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Belevych, A., Sansom, S., Terentyeva, R., Ho, H., Nishijima, Y., Martin, M., Jindal, H., Rochira, J., Kunitomo, Y., Abdellatif, M., Carnes, C., Elton, T., Gyorke, S., & Terenhyev, D. (2011). MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS One, 6(12), e28324. https://doi.org/10.1371/journal.pone.0028324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Lu, Y., Zhang, Y., Wang, N., Pan, Z., Gao, X., et al. (2010). MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation, 122, 2378–2387.

    CAS  PubMed  Google Scholar 

  155. Arslan, F., Lai, R., Smeets, M., Akeroyd, L., Choo, A., Aguor, E., Timmers, L., van Rijen, H., Doevendans, P., Pasterkamp, G., Lim, S., & de Kleijn, D. (2013). Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Research, 10(3), 301–312. https://doi.org/10.1016/j.scr.2013.01.002.

    Article  CAS  PubMed  Google Scholar 

  156. Vandergriff, A., De Andrade, J., Tang, J., Hensley, M., Piedrahita, J., Caranasos, T., & Cheng, K. (2015). Intravenous cardiac stem cell-derived exosomes ameliorate cardiac dysfunction in doxorubicin induced dilated cardiomyopathy. Stem Cells Int, 960926. https://doi.org/10.1155/2015/960926.

  157. Tseliou, E., Fouad, J., Reich, H., Slipczuk, L., de Couto, G., Aminzadeh, M., Middleton, R., Valle, J., Weixin, L., & Marbán, E. (2015). Fibroblasts rendered antifibrotic, antiapoptotic, and angiogenic by priming with cardiosphere-derived extracellular membrane vesicles. Journal of the American College of Cardiology, 66(6), 599–611. https://doi.org/10.1016/j.jacc.2015.05.068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Kumar, S., Kim, C., & Simmons, R. (2014). Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis – “Mechanosensitive Athero-miRs”. Arterioscler Thromb Vasc Biol, 34(10), 2206–2216. https://doi.org/10.1161/ATVBAHA.114.303425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Zhan, R., Leng, X., Liu, X., Wang, X., Gong, J., Yan, L., Yang, W., Wang, W., & Qian, L.-J. (2009). Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochemical and Biophysical Research Communications, 387, 229–223. https://doi.org/10.1016/j.bbrc.2009.06.095.

    Article  CAS  PubMed  Google Scholar 

  160. Zhang, Y., Hu, Y.-W., Zheng, L., & Wang, Q. (2017). Characteristics and roles of exosomes in cardiovascular disease. DNA and Cell Biology, 36(3), 202–211. https://doi.org/10.1089/dna.2016.3496.

    Article  CAS  PubMed  Google Scholar 

  161. Gao, W., Liu, H., Yuan, J., Wu, C., Huang, D., Ma, Y., Zhu, J., Ma, L., Guo, J., Shi, H., Zou, Y., & Ge, J. (2016). Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-alpha mediated NF-kappaB pathway. Journal of Cellular and Molecular Medicine, 20(12), 2318–2327. https://doi.org/10.1111/jcmm.12923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Zakharova, L., Svetlova, M., & Fomina, A. (2007). T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. Journal of Cellular Physiology, 212, 174–181.

    CAS  PubMed  Google Scholar 

  163. Wei, Y., Nazari-Jahantigh, M., Chan, L., Zhu, M., Heyll, K., Corbalan-Campos, J., Hartmann, P., Thiemann, A., Weber, C., & Schober, A. (2013). The microrna-342-5p fosters inflammatory macrophage activation through an akt1- and microrna-155-dependent pathway during atherosclerosis. Circ., 127, 1609–1619.

    CAS  Google Scholar 

  164. Srikanthan, S., Li, W., Silverstein, R., & McIntyre, T. (2014). Exosome poly-ubiquitin inhibits platelet activation, downregulates CD36 and inhibits pro-atherothombotic cellular functions. Journal of Thrombosis and Haemostasis, 12, 1906–1917.

    CAS  PubMed  Google Scholar 

  165. Wang, Y., Xie, Y., Zhang, A., Wang, M., Fang, Z., & Zhang, J. (2019). Exosomes: an emerging factor in atherosclerosis. Biomedicine & Pharmacotherapy, 118, 109119.

    Google Scholar 

  166. Zernecke, A., Bidzhekov, K., Noels, H., Shagdarsuren, E., Gan, L., Denecke, B., Hristov, M., Köppel, T., Jahantigh, M., Lutgens, E., Wang, S., Olson, E., Schober, A., & Weber, C. (2009). Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal, 2(100), ra81. https://doi.org/10.1126/scisignal.2000610.

    Article  PubMed  Google Scholar 

  167. Hergenreider, E., Heydt, S., Tréguer, K., Boettger, T., Horrevoets, A., Zeiher, A., Scheffer, M., Frangakis, A., Yin, X., Mayr, M., Braun, T., Urbich, C., Boon, R., & Dimmeler, S. (2012). Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature Cell Biology, 14(3), 249–256. https://doi.org/10.1038/ncb2441.

    Article  CAS  PubMed  Google Scholar 

  168. Wang, K., Garmire, L., Young, A., Nguyen, P., Trinh, A., Subramaniam, S., Wang, N., Shyy, J., Li, Y., & Chien, S. (2010). Role of microrna-23b in flow-regulation of rb phosphorylation and endothelial cell growth. Pro Nat Acad Sci USA., 107, 3234–3239.

    CAS  Google Scholar 

  169. Fang, Y., & Davies, P. F. (2012). Site-specific microrna-92a regulation of kruppel-like factors 4 and 2 in atherosusceptible endothelium. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 979–987.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Kim, C., Kumar, S., Son, D., Jang, I., Griendling, K., & Jo, H. (2014). Prevention of abdominal aortic aneurysm by anti-microrna-712 or anti-microrna-205 in angiotensin ii-infused mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(7), 1412–1421. https://doi.org/10.1161/ATVBAHA.113.303134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Ni, C., Qiu, H., & Jo, H. (2011). Microrna-663 upregulated by oscillatory shear stress plays a role ininflammatory response of endothelial cells. The American Journal of Physiology, 300, H1762–H1769.

    CAS  Google Scholar 

  172. Son, D., Kumar, S., Takabe, W., Kim, C., Ni, C., Alberts-Grill, N., Jang, I., Kim, S., Kim, W., Won Kang, S., Baker, A., Woong Seo, J., Ferrara, K., & Jo, H. (2013). The atypical mechanosensitive microrna-712 derived from pre-ribosomal rna induces endothelial inflammation and atherosclerosis. Nature Communications, 4, 3000. https://doi.org/10.1038/ncomms4000.

    Article  CAS  PubMed  Google Scholar 

  173. Rotllan, N., Ramirez, C. M., Aryal, B., Esau, C., & Fernandez-Hernando, C. (2013). Therapeutic silencing of microrna-33 inhibits the progression of atherosclerosis in ldlr−/− mice--brief report. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 1973–1977.

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Rayner, K., Esau, C., Hussain, F., McDaniel, A., Marshall, S., van Gils, J., Ray, T., Sheedy, F., Goedeke, L., Liu, X., Khatsenko, O., Kaimal, V., Lees, C., Fernandez-Hernando, C., Fisher, E., Temel, R., & Moore, K. (2011). Inhibition of mir-33a/b in non-human primates raises plasma hdl and lowers vldl triglycerides. Nature., 478, 404–407.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Sun, H.-X., Zeng, D.-Y., Li, R.-T., Pang, R.-P., Yang, H., Hu, Y.-L., Zhang, W., Jiang, Y., Huang, L.-Y., Tang, Y.-B., Yan, G.-J., & Zhou, J.-G. (2012). Essential role of microrna-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension, 60, 1407–1414.

    CAS  PubMed  Google Scholar 

  176. Chistiakov, D., Sobenin, I., Orekhov, A., & Bobryshev, Y. (2015). Human miR-221/222 in physiological and atherosclerotic vascular remodeling. BioMed Research International, 2015, 354517. https://doi.org/10.1155/2015/354517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Wei, Y., Nazari-Jahantigh, M., Chan, L., Zhu, M., Heyll, K., Corbalan-Campos, J., Hartmann, P., Thiemann, A., Weber, C., & Schober, A. (2013). The microrna-342-5p fosters inflammatory macrophage activation through an akt1- and microrna-155-dependent pathway during atherosclerosis. Circ., 127, 1609–1619.

    CAS  Google Scholar 

  178. Fang, Y., Shi, C., Manduchi, E., Civelek, M., & Davies, P. (2010). Microrna-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proceedings of the National Academy of Sciences of the United States of America, 107, 13450–13455.

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Qin, X., Wang, X., Wang, Y., Tang, Z., Cui, Q., Xi, J., Li, Y., Chien, S., & Wang, N. (2010). Microrna-19a mediates the suppressive effect of laminar flow on cyclin d1 expression in human umbilical vein endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 107, 3240–3244.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Wang, K., Garmire, L., Young, A., Nguyen, P., Trinh, A., Subramaniam, S., Wang, N., Shyy, J., Li, Y., & Chien, S. (2010). Role of microrna-23b in flow-regulation of rb phosphorylation and endothelial cell growth. Proceedings of the National Academy of Sciences of the United States of America, 107, 3234–3239.

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Chen, K., Fan, W., Wang, X., Ke, X., Wu, G., & Hu, C. (2012). Microrna-101 mediates the suppressive effect of laminar shear stress on mtor expression in vascular endothelial cells. Biochem Biophys Com., 427, 138–142.

    CAS  Google Scholar 

  182. Hergenreider, E., Heydt, S., Treguer, K., Boettger, T., Horrevoets, A. J., Zeiher, A., Scheffer, M., Frangakis, A., Yin, X., Mayr, M., Braun, T., Urbich, C., Boon, R. A., & Dimmeler, S. (2012). Atheroprotective communication between endothelial cells and smooth muscle cells through mirnas. Nature Cell Biology, 14, 249–256.

    CAS  PubMed  Google Scholar 

  183. Lovren, F., Pan, Y., Quan, A., Singh, K., Shukla, P., Gupta, N., Steer, B., Ingram, A. J., Gupta, M., Alomran, M., Teoh, H., Marsden, P., & Verma, S. (2012). Microrna-145 targeted therapy reduces atherosclerosis. Circ., 126, S81–S90.

    CAS  Google Scholar 

  184. Tian, G., Tang, Y., He, P., Lv, Y., Ouyang, X., Zhao, G., Tang, S., Wu, J., Wang, J., Peng, J., Zhang, M., Li, Y., Cayabyab, F., Zheng, X., Zhang, D., Yin, W., & Tang, C. (2014). The effects of mir-467b on lipoprotein lipase (lpl) expression, pro-inflammatory cytokine, lipid levels and atherosclerotic lesions in apolipoprotein e knockout mice. Biochemical and Biophysical Research Communications, 443, 428–434.

    CAS  PubMed  Google Scholar 

  185. Wang, H., Zhu, H. Q., Wang, F., Zhou, Q., Gui, S. Y., & Wang, Y. (2013). Microrna-1 prevents high-fat diet-induced endothelial permeability in apoe knock-out mice. Molecular and Cellular Biochemistry, 378, 153–159.

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Soh, J., Iqbal, J., Queiroz, J., Fernandez-Hernando, C., & Hussain, M. (2013). Microrna-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nature Medicine, 19, 892–900.

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Hao, X., & Fan, H. (2017). Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. European Review for Medical and Pharmacological Sciences, 21, 2725–2733.

    PubMed  Google Scholar 

  188. de Aguiar, V. T., Tarling, E., Kim, T., Civelek, M., Baldan, A., Esau, C., & Edwards, P. (2013). Microrna-144 regulates hepatic atp binding cassette transporter a1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid × receptor. Circulation Research, 112, 1602–1612.

    Google Scholar 

  189. Cheng, H., Sivachandran, N., Lau, A., Boudreau, E., Zhao, J., Baltimore, D., Delgado-Olguin, P., Cybulsky, M., & Fish, J. (2013). Microrna-146 represses endothelial activation by inhibiting proinflammatory pathways. EMBO Molecular Medicine, 5, 949–966.

    CAS  PubMed Central  Google Scholar 

  190. Zhao, Y., Li, Y., Luo, P., Gao, Y., Yang, J., Lao, K.-H., Wang, G., Cockerill, G., Hu, Y., Xu, Q., Li, T., & Zeng, L. I. (2016). XBP1 splicing triggers miR-150 transfer from smooth muscle cells to endothelial cells via extracellular vesicles. Scientific Reports, 6, 28627. https://doi.org/10.1038/srep28627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Sun, X., He, S., Wara, A., Icli, B., Shvartz, E., Tesmenitsky, Y., Belkin, N., Li, D., Blackwell, T., Sukhova, G., Croce, K., & Feinberg, M. (2014). Systemic delivery of microrna-181b inhibits nuclear factor-kappab activation, vascular inflammation, and atherosclerosis in apolipoprotein e-deficient mice. Circulation Research, 114, 32–40.

    CAS  PubMed  Google Scholar 

  192. Wang, Y., Wang, H., Liao, Y., Tsai, P., Chen, K., Cheng, H., Lin, R., & Juo, S. (2012). Microrna-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation. Cardiovascular Research, 95, 517–526.

    CAS  PubMed  Google Scholar 

  193. Ong, S.-G., Lee, W., Huang, M., Dey, D., Kodo, K., Sachez-Freire, V., Gold, J., & Wu, J. (2014). Cross talk of combined gene and cell therapy in ischemic heart disease role of exosomal microRNA transfer. Circ., 130, S60–S69. https://doi.org/10.1161/CIRCULATIONAHA.113.007917.

    Article  CAS  Google Scholar 

  194. Wang, S., Liao, J., Huang, H., Yin, H., Yang, W., & Hu, M. (2018). miR-214 and miR-126 were associated with restoration of endothelial function in obesity after exercise and dietary intervention. Journal of Applied Biomedicine, 16, 34–39. https://doi.org/10.1016/j.jab.2017.10.003.

    Article  CAS  Google Scholar 

  195. Zhuang, G., Meng, C., Guo, X., Cheruku, P. S., Shi, L., Xu, H., Li, H., Wang, G., Evans, A. R., Safe, S., Wu, C., & Zhou, B. (2012). A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circ., 125(23), 2892–2903. https://doi.org/10.1161/CIRCULATIONAHA.111.087817.

    Article  CAS  Google Scholar 

  196. Gidlof, O., van der Brug, M., Ohman, J., Gilje, P., Olde, B., Wahlestedt, C., & Erlinge, D. (2013). Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood, 121(19), 3908–3917, S1-26. https://doi.org/10.1182/blood-2012-10-461798.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks the librarians of the James A. Haley Hospital/University of South Florida for their assistance in providing many of the articles cited in this manuscript.

Funding

This study was supported in part by a grant from the Children’s Cardiomyopathy Foundation (002016).

Author information

Authors and Affiliations

  1. University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL, 33612-3805, USA

    Robert J. Henning

Authors
  1. Robert J. Henning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert J. Henning.

Ethics declarations

Conflict of Interest

The author has received research grants from the Children’s Cardiomyopathy Foundation (002016).

Ethical Approval

This is a review article and does not contain studies by the author on either humans or animals.

Declaration

The author has no any actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence (bias) this work.

Additional information

Associate Editor Junjie Xiao oversaw the review of this article

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henning, R.J. Cardiovascular Exosomes and MicroRNAs in Cardiovascular Physiology and Pathophysiology. J. of Cardiovasc. Trans. Res. 14, 195–212 (2021). https://doi.org/10.1007/s12265-020-10040-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-020-10040-5

Keywords

Search

Navigation