Advertisement

Mammalian Genome

, Volume 30, Issue 9–10, pp 276–288 | Cite as

miR-129-5p improves cardiac function in rats with chronic heart failure through targeting HMGB1

  • Na XiaoEmail author
  • Jun Zhang
  • Chao Chen
  • Yanfang Wan
  • Ning Wang
  • Jing Yang
Article
  • 64 Downloads

Abstract

Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p in chronic heart failure and the underlying mechanisms. The levels of miR-129-5p and HMGB1 in chronic heart failure patients (CHF) and normal controls were examined by RT-qPCR and ELISA. Cardiac function, hemodynamics parameters, oxidative stress, and inflammation factors were analyzed in CHF rat model after transfection of miR-129-5p or HMGB1. Dual-luciferase activity reporter assay was conducted to validate the interaction between miR-129-5p and HMGB1. Downregulation of miR-129-5p and upregulation of HMGB1 were observed in the serum of CHF patients, respectively. Transfection of miR-129-5p improved heart function and hemodynamic parameters, as well as attenuated oxidative stress and inflammation factors in CHF rats. We further confirmed that HMGB1 is a direct target of miR-129-5p. Transfection of miR-129-5p also decreased the mRNA and protein levels of HMGB1 in myocardial tissues of CHF rats. Overexpression of HMGB1 diminished the effects of miR-129-5p on ameliorating oxidative stress and inflammatory response in rats with CHF. Our findings suggest that miR-129-5p protects the heart by targeting HMGB1.

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All participants in this study were informed and gave a written consent.

Research involving human participants and/or animals

The protocols were approved by the Ethics Committee of Cangzhou Central Hospital, and all participants signed informed consent.

References

  1. Aspromonte N et al (2017) ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure. European Heart Journal Supplements 19:D102–D112.  https://doi.org/10.1093/eurheartj/sux027 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Azad N, Lemay G (2014) Management of chronic heart failure in the older population. J Geriatr Cardiol 11:329–337.  https://doi.org/10.11909/j.issn.1671-5411.2014.04.008 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V (2019) How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC 30:114–127PubMedPubMedCentralGoogle Scholar
  4. Buscaglia LE, Li Y (2011) Apoptosis and the target genes of microRNA-21. Chin J Cancer 30:371–380CrossRefGoogle Scholar
  5. Choi HM, Park MS, Youn JC (2019) Update on heart failure management and future directions. Korean J Intern Med 34:11–43.  https://doi.org/10.3904/kjim.2018.428 CrossRefPubMedGoogle Scholar
  6. Dinatolo E, Sciatti E, Anker MS, Lombardi C, Dasseni N, Metra M (2018) Updates in heart failure: what last year brought to us. ESC Heart Fail 5:989–1007.  https://doi.org/10.1002/ehf2.12385 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Elahi MM, Kong YX, Matata BM (2009) Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev 2:259–269.  https://doi.org/10.4161/oxim.2.5.9441 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Funahashi H, Izawa H, Hirashiki A, Cheng XW, Inden Y, Nomura M, Murohara T (2011) Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure. J Cardiol 57:338–344.  https://doi.org/10.1016/j.jjcc.2011.01.009 CrossRefPubMedGoogle Scholar
  9. Hu H, Zhang Y, Shi Y, Feng L, Duan J, Sun Z (2017) Microarray-based bioinformatics analysis of the combined effects of SiNPs and PbAc on cardiovascular system in zebrafish. Chemosphere 184:1298–1309.  https://doi.org/10.1016/j.chemosphere.2017.06.112 CrossRefPubMedGoogle Scholar
  10. Huang YM, Li WW, Wu J, Han M, Li BH (2019) The diagnostic value of circulating microRNAs in heart failure. Exp Ther Med 17:1985–2003.  https://doi.org/10.3892/etm.2019.7177 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP (2017) Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals.  https://doi.org/10.3390/ph11010002 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Inamdar AA, Inamdar AC (2016) Heart failure: diagnosis, management and utilization. J Clin Med.  https://doi.org/10.3390/jcm5070062 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kalogeropoulos AP, Georgiopoulou VV, Butler J (2012) Clinical adoption of prognostic biomarkers: the case for heart failure. Prog Cardiovasc Dis 55:3–13.  https://doi.org/10.1016/j.pcad.2012.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Li W, Sama AE, Wang H (2006) Role of HMGB1 in cardiovascular diseases. Curr Opin Pharmacol 6:130–135.  https://doi.org/10.1016/j.coph.2005.10.010 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Li XQ, Chen FS, Tan WF, Fang B, Zhang ZL, Ma H (2017) Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway. J Neuroinflamm 14:205.  https://doi.org/10.1186/s12974-017-0977-4 CrossRefGoogle Scholar
  16. Li G, Xie J, Wang J (2019) Tumor suppressor function of miR-129-5p in lung cancer. Oncol Lett 17:5777–5783.  https://doi.org/10.3892/ol.2019.10241 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Luo J, Chen J, He L (2015) mir-129-5p attenuates irradiation-induced autophagy and decreases radioresistance of breast cancer cells by targeting HMGB1 medical science monitor. Int Med J Exp Clin Res 21:4122–4129.  https://doi.org/10.12659/msm.896661 CrossRefGoogle Scholar
  18. Ma XL, Li SY, Shang F (2017) Effect of microRNA-129-5p targeting HMGB1-RAGE signaling pathway on revascularization in a collagenase-induced intracerebral hemorrhage rat model. Biomed Pharmacother 93:238–244.  https://doi.org/10.1016/j.biopha.2017.06.012 CrossRefPubMedGoogle Scholar
  19. Martinotti S, Patrone M, Ranzato E (2015) Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. ImmunoTargets Therapy 4:101–109.  https://doi.org/10.2147/ITT.S58064 CrossRefPubMedGoogle Scholar
  20. Motiejunaite J, Chouihed T, Mebazaa A (2017) Upcoming challenges in multidisciplinary heart failure management: active role of future clinical pharmacists. Clin Pharmacol Ther 102:180–182.  https://doi.org/10.1002/cpt.728 CrossRefPubMedGoogle Scholar
  21. Mukhopadhyay P, Eid N, Abdelmegeed MA, Sen A (2018) Interplay of oxidative stress, inflammation, and autophagy: their role in tissue injury of the heart, liver, and kidney. Oxid Med Cell Longev 2018:2090813.  https://doi.org/10.1155/2018/2090813 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Murach KA, McCarthy JJ (2017) MicroRNAs, heart failure, and aging: potential interactions with skeletal muscle. Heart Fail Rev 22:209–218.  https://doi.org/10.1007/s10741-016-9572-5 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Oikonomou E et al (2013) Diagnostic and therapeutic potentials of microRNAs in heart failure. Curr Top Med Chem 13:1548–1558CrossRefGoogle Scholar
  24. Pan Z et al (2012) miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS ONE 7:e50515.  https://doi.org/10.1371/journal.pone.0050515 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Pashkow FJ (2011) Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int J Inflamm 2011:514623.  https://doi.org/10.4061/2011/514623 CrossRefGoogle Scholar
  26. Qin Y, Yu Y, Dong H, Bian X, Guo X, Dong S (2012) MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis. Int J Med Sci 9:413–423.  https://doi.org/10.7150/ijms.4514 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Ramachandran S, Lowenthal A, Ritner C, Lowenthal S, Bernstein HS (2017) Plasma microvesicle analysis identifies microRNA 129-5p as a biomarker of heart failure in univentricular heart disease. PLoS ONE 12:e0183624.  https://doi.org/10.1371/journal.pone.0183624 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ramani GV, Uber PA, Mehra MR (2010) Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc 85:180–195.  https://doi.org/10.4065/mcp.2009.0494 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Raucci A, Di Maggio S, Scavello F, D’Ambrosio A, Bianchi ME, Capogrossi MC (2019) The Janus face of HMGB1 in heart disease: a necessary update. Cell Mol Life Sci 76:211–229.  https://doi.org/10.1007/s00018-018-2930-9 CrossRefPubMedGoogle Scholar
  30. Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126.  https://doi.org/10.1146/annurev.pathmechdis.3.121806.151456 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Savarese G, Lund LH (2017) Global public health burden of heart failure. Cardiac Fail Rev 3:7–11.  https://doi.org/10.15420/cfr.2016:25:2 CrossRefGoogle Scholar
  32. Shah RV, Das S, Lewis GD (2019) Circulating microRNAs: new avenues for heart failure classification? J Am Coll Cardiol 73:1314–1316.  https://doi.org/10.1016/j.jacc.2018.10.091 CrossRefPubMedGoogle Scholar
  33. Silva D, Carneiro FD, Almeida KC, Fernandes-Santos C (2018) Role of miRNAs on the pathophysiology of cardiovascular diseases. Arq Bras Cardiol 111:738–746.  https://doi.org/10.5935/abc.20180215 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Verjans R et al (2019) Functional screening identifies micrornas as multi-cellular regulators of heart failure. Scientific Reports 9:6055.  https://doi.org/10.1038/s41598-019-41491-9 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Voellenkle C et al (2010) MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genom 42:420–426.  https://doi.org/10.1152/physiolgenomics.00211.2009 CrossRefGoogle Scholar
  36. Volz HC et al (2012) HMGB1 is an independent predictor of death and heart transplantation in heart failure. Clin Res Cardiol 101:427–435.  https://doi.org/10.1007/s00392-011-0409-x CrossRefPubMedGoogle Scholar
  37. Wang S, Chen Y, Yu X, Lu Y, Wang H, Wu F, Teng L (2019) miR-129-5p attenuates cell proliferation and epithelial mesenchymal transition via HMGB1 in gastric cancer. Pathol Res Pract 215:676–682.  https://doi.org/10.1016/j.prp.2018.12.024 CrossRefPubMedGoogle Scholar
  38. Welsh P et al (2018) Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study. Eur J Heart Fail 20:268–277.  https://doi.org/10.1002/ejhf.988 CrossRefPubMedGoogle Scholar
  39. Wu Q, Meng WY, Jie Y, Zhao H (2018) LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis. J Cell Physiol 233:6750–6757.  https://doi.org/10.1002/jcp.26383 CrossRefPubMedGoogle Scholar
  40. Yan H et al (2017) miRNAs as biomarkers for diagnosis of heart failure: a systematic review and meta-analysis. Medicine 96:e6825.  https://doi.org/10.1097/MD.0000000000006825 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Yang Y et al (2017) miRNAs as potential therapeutic targets and diagnostic biomarkers for cardiovascular disease with a particular focus on WO2010091204. Expert Opin Ther Pat 27:1021–1029.  https://doi.org/10.1080/13543776.2017.1344217 CrossRefPubMedGoogle Scholar
  42. Yang L, Wang B, Zhou Q, Wang Y, Liu X, Liu Z, Zhan Z (2018) MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7. Cell Death Dis 9:769.  https://doi.org/10.1038/s41419-018-0805-5 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Yao HC et al (2016) Intravenous high mobility group box 1 upregulates the expression of HIF-1alpha in the myocardium via a protein kinase B-dependent pathway in rats following acute myocardial ischemia. Mol Med Rep 13:1211–1219.  https://doi.org/10.3892/mmr.2015.4648 CrossRefPubMedGoogle Scholar
  44. Zhang D et al (2017a) Long noncoding RNA PCAT-1 promotes invasion and metastasis via the miR-129-5p-HMGB1 signaling pathway in hepatocellular carcinoma. Biomed Pharmacother 95:1187–1193.  https://doi.org/10.1016/j.biopha.2017.09.045 CrossRefPubMedGoogle Scholar
  45. Zhang J et al (2017b) Circulating miRNA21 is a promising biomarker for heart failure. Mol Med Rep 16:7766–7774.  https://doi.org/10.3892/mmr.2017.7575 CrossRefPubMedGoogle Scholar
  46. Zhang H, Zhang X, Zhang J (2018) MiR-129-5p inhibits autophagy and apoptosis of H9c2 cells induced by hydrogen peroxide via the PI3K/AKT/mTOR signaling pathway by targeting ATG14. Biochem Biophys Res Commun 506:272–277.  https://doi.org/10.1016/j.bbrc.2018.10.085 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Na Xiao
    • 1
    Email author
  • Jun Zhang
    • 1
  • Chao Chen
    • 1
  • Yanfang Wan
    • 1
  • Ning Wang
    • 1
  • Jing Yang
    • 1
  1. 1.Department Cardiovascular VCangzhou Central HospitalCangzhouChina

Personalised recommendations