Skip to main content
SpringerLink
Log in
Book cover

Epicardial Adipose Tissue pp 19–36Cite as

Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue

  • Chapter
  • First Online:

  • 488 Accesses

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

The study of epicardial adipose tissue (EAT) has been limited by its accessibility due to its proximity to the heart. Moreover, many common animal models do not have EAT, leaving its functional role underestimated and poorly elucidated. Recent advances in medicine and science have allowed for better studies that provide a more comprehensive understanding of its physiological role. One way to dissect its function is the study of its gene expression. In this chapter, we summarize transcriptomic and proteomic analyses which show that EAT expresses a unique set of genes setting it apart from other adipose tissues in the body. This distinctive set of genes modulates a feedback mechanism that has direct interaction with the myocardium. The EAT shares its blood supply with the coronary arteries and innervation with the cardiac muscle, provides physical protection, and regulates energetic metabolites needed by the myocardium. Transcriptomic and proteomic studies show that it is a local source of adipokines with paracrine influence on the myocardium due to the intimate microcirculation shared by both tissues. These analyses also show that it has a role in the immune and endocrine systems affecting the rest of the body. Furthermore, regulation of EAT gene expression is not monolithic and can be affected by multiple factors such as sex, age, underling disease, medication, etc. Gene expression studies can therefore provide great insight into the function of EAT and its role in health and disease.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab. 2018;27:68–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kajimura S, Spiegelman BM, Seale P. Brown and beige fat: physiological roles beyond heat generation. Cell Metab. 2015;22:546–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gupta RK. Adipocytes. Curr Biol. 2014;24:R988–93.

    Article  CAS  PubMed  Google Scholar 

  4. Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36:461–70.

    Article  CAS  PubMed  Google Scholar 

  5. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab. 2011;22:450–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Iacobellis G, Barbaro G. Epicardial adipose tissue feeding and overfeeding the heart. Nutrition. 2019;59:1–6.

    Article  CAS  PubMed  Google Scholar 

  7. Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22:1311–9. quiz 1417-8

    Article  PubMed  Google Scholar 

  8. Talman AH, Psaltis PJ, Cameron JD, Meredith IT, Seneviratne SK, Wong DT. Epicardial adipose tissue: far more than a fat depot. Cardiovasc Diagn Ther. 2014;4:416–29.

    PubMed  PubMed Central  Google Scholar 

  9. Marchington JM, Mattacks CA, Pond CM. Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. Comp Biochem Physiol B. 1989;94:225–32.

    Article  CAS  PubMed  Google Scholar 

  10. Swifka J, Weiss J, Addicks K, Eckel J, Rosen P. Epicardial fat from guinea pig: a model to study the paracrine network of interactions between epicardial fat and myocardium? Cardiovasc Drugs Ther. 2008;22:107–14.

    Article  PubMed  Google Scholar 

  11. Greulich S, de Wiza DH, Preilowski S, Ding Z, Mueller H, Langin D, et al. Secretory products of guinea pig epicardial fat induce insulin resistance and impair primary adult rat cardiomyocyte function. J Cell Mol Med. 2011;15:2399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Company JM, Booth FW, Laughlin MH, Arce-Esquivel AA, Sacks HS, Bahouth SW, et al. Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat. J Appl Physiol (1985). 2010;109:1904–12.

    Article  Google Scholar 

  13. Chilukoti RK, Giese A, Malenke W, Homuth G, Bukowska A, Goette A, et al. Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. Int J Cardiol. 2015;187:604–13.

    Article  CAS  PubMed  Google Scholar 

  14. Antonopoulos AS, Margaritis M, Verheule S, Recalde A, Sanna F, Herdman L, et al. Mutual regulation of epicardial adipose tissue and myocardial redox state by PPAR-gamma/adiponectin signaling. Circ Res. 2016;118(5):842–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Oclon E, Latacz A, Zubel-Lojek J, Pierzchala-Koziec K. Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets. J Endocrinol. 2016;229:259–66.

    Article  CAS  PubMed  Google Scholar 

  16. Distel E, Penot G, Cadoudal T, Balguy I, Durant S, Benelli C. Early induction of a brown-like phenotype by rosiglitazone in the epicardial adipose tissue of fatty Zucker rats. Biochimie. 2012;94:1660–7.

    Article  CAS  PubMed  Google Scholar 

  17. Yamaguchi Y, Cavallero S, Patterson M, Shen H, Xu J, Kumar SR, et al. Adipogenesis and epicardial adipose tissue: a novel fate of the epicardium induced by mesenchymal transformation and PPARgamma activation. Proc Natl Acad Sci U S A. 2015;112:2070–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Langheim S, Dreas L, Veschini L, Maisano F, Foglieni C, Ferrarello S, et al. Increased expression and secretion of resistin in epicardial adipose tissue of patients with acute coronary syndrome. Am J Physiol Heart Circ Physiol. 2010;298:H746–53.

    Article  PubMed  Google Scholar 

  19. Karastergiou K, Evans I, Ogston N, Miheisi N, Nair D, Kaski JC, et al. Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells. Arterioscler Thromb Vasc Biol. 2010;30:1340–6.

    Article  CAS  PubMed  Google Scholar 

  20. Fernandez-Trasancos A, Guerola-Segura R, Paradela-Dobarro B, Alvarez E, Garcia-Acuna JM, Fernandez AL, et al. Glucose and inflammatory cells decrease adiponectin in epicardial adipose tissue cells: paracrine consequences on vascular endothelium. J Cell Physiol. 2016;231:1015–23.

    Article  CAS  PubMed  Google Scholar 

  21. Viviano A, Yin X, Zampetaki A, Fava M, Gallagher M, Mayr M, et al. Proteomics of the epicardial fat secretome and its role in post-operative atrial fibrillation. Europace. 2018;20:1201–8.

    Article  PubMed  Google Scholar 

  22. Gruzdeva OV, Akbasheva OE, Dyleva YA, Antonova LV, Matveeva VG, Uchasova EG, et al. Adipokine and cytokine profiles of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Bull Exp Biol Med. 2017;163:608–11.

    Article  CAS  PubMed  Google Scholar 

  23. Chechi K, Voisine P, Mathieu P, Laplante M, Bonnet S, Picard F, et al. Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue. Sci Rep. 2017;7:15566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Furuhashi M, Fuseya T, Murata M, Hoshina K, Ishimura S, Mita T, et al. Local production of fatty acid-binding protein 4 in epicardial/perivascular fat and macrophages is linked to coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2016;36:825–34.

    Article  CAS  PubMed  Google Scholar 

  25. Kremen J, Dolinkova M, Krajickova J, Blaha J, Anderlova K, Lacinova Z, et al. Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance. J Clin Endocrinol Metab. 2006;91:4620–7.

    Article  CAS  PubMed  Google Scholar 

  26. Silaghi A, Achard V, Paulmyer-Lacroix O, Scridon T, Tassistro V, Duncea I, et al. Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status. Am J Physiol Endocrinol Metab. 2007;293:E1443–50.

    Article  CAS  PubMed  Google Scholar 

  27. Roubicek T, Dolinkova M, Blaha J, Haluzikova D, Bosanska L, Mraz M, et al. Increased angiotensinogen production in epicardial adipose tissue during cardiac surgery: possible role in a postoperative insulin resistance. Physiol Res. 2008;57:911–7.

    CAS  PubMed  Google Scholar 

  28. Kotulak T, Drapalova J, Kopecky P, Lacinova Z, Kramar P, Riha H, et al. Increased circulating and epicardial adipose tissue mRNA expression of fibroblast growth factor-21 after cardiac surgery: possible role in postoperative inflammatory response and insulin resistance. Physiol Res. 2011;60:757–67.

    Article  CAS  PubMed  Google Scholar 

  29. Kotulak T, Drapalova J, Lips M, Lacinova Z, Kramar P, Riha H, et al. Cardiac surgery increases serum concentrations of adipocyte fatty acid-binding protein and its mRNA expression in circulating monocytes but not in adipose tissue. Physiol Res. 2014;63:83–94.

    CAS  PubMed  Google Scholar 

  30. Eiras S, Teijeira-Fernandez E, Salgado-Somoza A, Couso E, Garcia-Caballero T, Sierra J, et al. Relationship between epicardial adipose tissue adipocyte size and MCP-1 expression. Cytokine. 2010;51:207–12.

    Article  CAS  PubMed  Google Scholar 

  31. Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes. 1995;44:855–8.

    Article  CAS  PubMed  Google Scholar 

  32. Arner P. Regional differences in protein production by human adipose tissue. Biochem Soc Trans. 2001;29:72–5.

    Article  CAS  PubMed  Google Scholar 

  33. Dusserre E, Moulin P, Vidal H. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta. 2000;1500:88–96.

    Article  CAS  PubMed  Google Scholar 

  34. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108:2460–6.

    Article  PubMed  Google Scholar 

  35. Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29:251–5.

    CAS  PubMed  Google Scholar 

  36. Date H, Imamura T, Ideguchi T, Kawagoe J, Sumi T, Masuyama H, et al. Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries. Clin Cardiol. 2006;29:211–4.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Iglesias MJ, Eiras S, Pineiro R, Lopez-Otero D, Gallego R, Fernandez AL, et al. Gender differences in adiponectin and leptin expression in epicardial and subcutaneous adipose tissue. Findings in patients undergoing cardiac surgery. Rev Esp Cardiol. 2006;59:1252–60.

    Article  PubMed  Google Scholar 

  39. Cheng KH, Chu CS, Lee KT, Lin TH, Hsieh CC, Chiu CC, et al. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int J Obes. 2008;32:268–74.

    Article  CAS  Google Scholar 

  40. Eiras S, Teijeira-Fernandez E, Shamagian LG, Fernandez AL, Vazquez-Boquete A, Gonzalez-Juanatey JR. Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue. Cytokine. 2008;43:174–80.

    Article  CAS  PubMed  Google Scholar 

  41. Fain JN, Sacks HS, Buehrer B, Bahouth SW, Garrett E, Wolf RY, et al. Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots. Int J Obes. 2008;32:810–5.

    Article  CAS  Google Scholar 

  42. Madani R, Karastergiou K, Ogston NC, Miheisi N, Bhome R, Haloob N, et al. RANTES release by human adipose tissue in vivo and evidence for depot-specific differences. Am J Physiol Endocrinol Metab. 2009;296:E1262–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shibasaki I, Nishikimi T, Mochizuki Y, Yamada Y, Yoshitatsu M, Inoue Y, et al. Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic peptide receptor-C in epicardial adipose tissue in coronary artery disease. Regul Pept. 2010;165:210–7.

    Article  CAS  PubMed  Google Scholar 

  44. Ji Q, Zhang J, Du Y, Zhu E, Wang Z, Que B, et al. Human epicardial adipose tissue-derived and circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with coronary artery disease. Cardiovasc Diabetol. 2017;16:133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Baker AR, Harte AL, Howell N, Pritlove DC, Ranasinghe AM, da Silva NF, et al. Epicardial adipose tissue as a source of nuclear factor-kappaB and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease. J Clin Endocrinol Metab. 2009;94:261–7.

    Article  CAS  PubMed  Google Scholar 

  46. Salgado-Somoza A, Teijeira-Fernandez E, Fernandez AL, Gonzalez-Juanatey JR, Eiras S. Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress. Am J Physiol Heart Circ Physiol. 2010;299:H202–9.

    Article  CAS  PubMed  Google Scholar 

  47. Rodino-Janeiro BK, Salgado-Somoza A, Teijeira-Fernandez E, Gonzalez-Juanatey JR, Alvarez E, Eiras S. Receptor for advanced glycation end-products expression in subcutaneous adipose tissue is related to coronary artery disease. Eur J Endocrinol. 2011;164:529–37.

    Article  CAS  PubMed  Google Scholar 

  48. Jaffer I, Riederer M, Shah P, Peters P, Quehenberger F, Wood A, et al. Expression of fat mobilizing genes in human epicardial adipose tissue. Atherosclerosis. 2012;220:122–7.

    Article  CAS  PubMed  Google Scholar 

  49. Chechi K, Blanchard PG, Mathieu P, Deshaies Y, Richard D. Brown fat like gene expression in the epicardial fat depot correlates with circulating HDL-cholesterol and triglycerides in patients with coronary artery disease. Int J Cardiol. 2013;167:2264–70.

    Article  PubMed  Google Scholar 

  50. Burgeiro A, Fonseca AC, Espinoza D, Carvalho L, Lourenco N, Antunes M, et al. Proteostasis in epicardial versus subcutaneous adipose tissue in heart failure subjects with and without diabetes. Biochim Biophys Acta Mol basis Dis. 2018;1864:2183–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Salgado-Somoza A, Teijeira-Fernandez E, Fernandez AL, Gonzalez-Juanatey JR, Eiras S. Changes in lipid transport-involved proteins of epicardial adipose tissue associated with coronary artery disease. Atherosclerosis. 2012;224:492–9.

    Article  CAS  PubMed  Google Scholar 

  52. Blumensatt M, Greulich S, Herzfeld de Wiza D, Mueller H, Maxhera B, Rabelink MJ, et al. Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143. Cardiovasc Res. 2013;100:201–10.

    Article  CAS  PubMed  Google Scholar 

  53. Agra RM, Teijeira-Fernandez E, Pascual-Figal D, Jesus SM, Fernandez-Trasancos A, Sierra J, et al. Differential behavior between S100A9 and adiponectin in coronary artery disease. Plasma or epicardial fat. Life Sci. 2014;100:147–51.

    Article  CAS  PubMed  Google Scholar 

  54. Rachwalik M, Zysko D, Diakowska D, Kustrzycki W. Increased content of resistin in epicardial adipose tissue of patients with advanced coronary atherosclerosis and history of myocardial infarction. Thorac Cardiovasc Surg. 2014;62:554–60.

    Article  PubMed  Google Scholar 

  55. Fandino-Vaquero R, Fernandez-Trasancos A, Alvarez E, Ahmad S, Batista-Oliveira AL, Adrio B, et al. Orosomucoid secretion levels by epicardial adipose tissue as possible indicator of endothelial dysfunction in diabetes mellitus or inflammation in coronary artery disease. Atherosclerosis. 2014;235:281–8.

    Article  CAS  PubMed  Google Scholar 

  56. Obokata M, Iso T, Ohyama Y, Sunaga H, Kawaguchi T, Matsui H, et al. Early increase in serum fatty acid binding protein 4 levels in patients with acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2018;7:561–9.

    Article  PubMed  Google Scholar 

  57. Conover CA, Bale LK, Frye RL, Schaff HV. Cellular characterization of human epicardial adipose tissue: highly expressed PAPP-A regulates insulin-like growth factor I signaling in human cardiomyocytes. Physiol Rep. 2019;7:e14006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Guauque-Olarte S, Gaudreault N, Piche ME, Fournier D, Mauriege P, Mathieu P, et al. The transcriptome of human epicardial, mediastinal and subcutaneous adipose tissues in men with coronary artery disease. PLoS One. 2011;6:e19908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Imoto-Tsubakimoto H, Takahashi T, Ueyama T, Ogata T, Adachi A, Nakanishi N, et al. Serglycin is a novel adipocytokine highly expressed in epicardial adipose tissue. Biochem Biophys Res Commun. 2013;432:105–10.

    Article  CAS  PubMed  Google Scholar 

  60. McAninch EA, Fonseca TL, Poggioli R, Panos AL, Salerno TA, Deng Y, et al. Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease. Obesity (Silver Spring). 2015;23:1267–78.

    Article  CAS  PubMed Central  Google Scholar 

  61. Gaborit B, Venteclef N, Ancel P, Pelloux V, Gariboldi V, Leprince P, et al. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovasc Res. 2015;108:62–73.

    Article  CAS  PubMed  Google Scholar 

  62. Vacca M, Di Eusanio M, Cariello M, Graziano G, D’Amore S, Petridis FD, et al. Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis. Cardiovasc Res. 2016;109:228–39.

    Article  CAS  PubMed  Google Scholar 

  63. Camarena V, Sant D, Mohseni M, Salerno T, Zaleski ML, Wang G, et al. Novel atherogenic pathways from the differential transcriptome analysis of diabetic epicardial adipose tissue. Nutr Metab Cardiovasc Dis. 2017;27:739–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chechi K, Vijay J, Voisine P, Mathieu P, Bosse Y, Tchernof A, et al. UCP1 expression-associated gene signatures of human epicardial adipose tissue. JCI Insight. 2019;4. https://doi.org/10.1172/jci.insight.123618.

  65. Tomasova P, Cermakova M, Pelantova H, Vecka M, Kratochvilova H, Lips M, et al. Minor lipids profiling in subcutaneous and epicardial fat tissue using LC/MS with an optimized preanalytical phase. J Chromatogr B Analyt Technol Biomed Life Sci. 2019;1113:50–9.

    Article  CAS  PubMed  Google Scholar 

  66. Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res. 2004;146:279–89.

    Article  CAS  PubMed  Google Scholar 

  67. Iacobellis G, di Gioia CR, Cotesta D, Petramala L, Travaglini C, De Santis V, et al. Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels. Horm Metab Res. 2009;41:227–31.

    Article  CAS  PubMed  Google Scholar 

  68. Iacobellis G, di Gioia CR, Di Vito M, Petramala L, Cotesta D, De Santis V, et al. Epicardial adipose tissue and intracoronary adrenomedullin levels in coronary artery disease. Horm Metab Res. 2009;41:855–60.

    Article  CAS  PubMed  Google Scholar 

  69. Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb. 2010;17:115–30.

    Article  CAS  PubMed  Google Scholar 

  70. Iacobellis G. Epicardial and pericardial fat: close, but very different. Obesity (Silver Spring). 2009;17:625; author reply 626–7.

    Article  Google Scholar 

  71. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med. 2005;2:536–43.

    Article  PubMed  Google Scholar 

  72. Gao X, Mi S, Zhang F, Gong F, Lai Y, Gao F, et al. Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. Cardiovasc Diabetol. 2011;10:87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, et al. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2013;33:1077–84.

    Article  CAS  PubMed  Google Scholar 

  74. Dozio E, Malavazos AE, Vianello E, Briganti S, Dogliotti G, Bandera F, et al. Interleukin-15 and soluble interleukin-15 receptor alpha in coronary artery disease patients: association with epicardial fat and indices of adipose tissue distribution. PLoS One. 2014;9:e90960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mitchell JD, Maguire JJ, Kuc RE, Davenport AP. Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system. Cardiovasc Res. 2009;81:353–61.

    Article  CAS  PubMed  Google Scholar 

  76. Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z, et al. Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol. 2011;10:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Fernandez-Trasancos A, Fandino-Vaquero R, Agra RM, Fernandez AL, Vinuela JE, Gonzalez-Juanatey JR, et al. Impaired adipogenesis and insulin resistance in epicardial fat-mesenchymal cells from patients with cardiovascular disease. J Cell Physiol. 2014;229:1722–30.

    Article  CAS  PubMed  Google Scholar 

  78. Fernandez-Trasancos A, Agra RM, Garcia-Acuna JM, Fernandez AL, Gonzalez-Juanatey JR, Eiras S. Omentin treatment of epicardial fat improves its anti-inflammatory activity and paracrine benefit on smooth muscle cells. Obesity (Silver Spring). 2017;25:1042–9.

    Article  CAS  Google Scholar 

  79. Blumensatt M, Fahlbusch P, Hilgers R, Bekaert M, Herzfeld de Wiza D, Akhyari P, et al. Secretory products from epicardial adipose tissue from patients with type 2 diabetes impair mitochondrial beta-oxidation in cardiomyocytes via activation of the cardiac renin-angiotensin system and induction of miR-208a. Basic Res Cardiol. 2017;112:2.

    Article  CAS  PubMed  Google Scholar 

  80. Malavazos AE, Ermetici F, Coman C, Corsi MM, Morricone L, Ambrosi B. Influence of epicardial adipose tissue and adipocytokine levels on cardiac abnormalities in visceral obesity. Int J Cardiol. 2007;121:132–4.

    Article  PubMed  Google Scholar 

  81. Dozio E, Dogliotti G, Malavazos AE, Bandera F, Cassetti G, Vianello E, et al. IL-18 level in patients undergoing coronary artery bypass grafting surgery or valve replacement: which link with epicardial fat depot? Int J Immunopathol Pharmacol. 2012;25:1011–20.

    Article  CAS  PubMed  Google Scholar 

  82. Wang Q, Shen H, Min J, Gao Y, Liu K, Xi W, et al. YKL-40 is highly expressed in the epicardial adipose tissue of patients with atrial fibrillation and associated with atrial fibrosis. J Transl Med. 2018;16:229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Jiang DS, Zeng HL, Li R, Huo B, Su YS, Fang J, et al. Aberrant epicardial adipose tissue extracellular matrix remodeling in patients with severe ischemic cardiomyopathy: insight from comparative quantitative proteomics. Sci Rep. 2017;7:43787.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Vianello E, Dozio E, Arnaboldi F, Marazzi MG, Martinelli C, Lamont J, et al. Epicardial adipocyte hypertrophy: association with M1-polarization and toll-like receptor pathways in coronary artery disease patients. Nutr Metab Cardiovasc Dis. 2016;26:246–53.

    Article  CAS  PubMed  Google Scholar 

  85. Andersen JK, Oma I, Prayson RA, Kvelstad IL, Almdahl SM, Fagerland MW, et al. Inflammatory cell infiltrates in the heart of patients with coronary artery disease with and without inflammatory rheumatic disease: a biopsy study. Arthritis Res Ther. 2016;18:232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hirata Y, Kurobe H, Akaike M, Chikugo F, Hori T, Bando Y, et al. Enhanced inflammation in epicardial fat in patients with coronary artery disease. Int Heart J. 2011;52:139–42.

    Article  CAS  PubMed  Google Scholar 

  87. Gurses KM, Ozmen F, Kocyigit D, Yersal N, Bilgic E, Kaya E, et al. Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease. J Cardiol. 2017;69:851–8.

    Article  PubMed  Google Scholar 

  88. Miksztowicz V, Morales C, Barchuk M, Lopez G, Poveda R, Gelpi R, et al. Metalloproteinase 2 and 9 activity increase in epicardial adipose tissue of patients with coronary artery disease. Curr Vasc Pharmacol. 2017;15:135–43.

    Article  CAS  PubMed  Google Scholar 

  89. Mraz M, Cinkajzlova A, Klouckova J, Lacinova Z, Kratochvilova H, Lips M, et al. Dendritic cells in subcutaneous and epicardial adipose tissue of subjects with type 2 diabetes, obesity, and coronary artery disease. Mediat Inflamm. 2019;2019:5481725.

    Google Scholar 

  90. Pedicino D, Severino A, Ucci S, Bugli F, Flego D, Giglio AF, et al. Epicardial adipose tissue microbial colonization and inflammasome activation in acute coronary syndrome. Int J Cardiol. 2017;236:95–9.

    Article  PubMed  Google Scholar 

  91. White UA, Tchoukalova YD. Sex dimorphism and depot differences in adipose tissue function. Biochim Biophys Acta. 2014;1842:377–92.

    Article  CAS  PubMed  Google Scholar 

  92. Chang E, Varghese M, Singer K. Gender and sex differences in adipose tissue. Curr Diab Rep. 2018;18:69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Palmer AK, Kirkland JL. Aging and adipose tissue: potential interventions for diabetes and regenerative medicine. Exp Gerontol. 2016;86:97–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Niemann B, Pan R, Teschner M, Boening A, Silber RE, Rohrbach S. Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue. Exp Gerontol. 2013;48:55–63.

    Article  CAS  PubMed  Google Scholar 

  95. Dutour A, Achard V, Sell H, Naour N, Collart F, Gaborit B, et al. Secretory type II phospholipase A2 is produced and secreted by epicardial adipose tissue and overexpressed in patients with coronary artery disease. J Clin Endocrinol Metab. 2010;95:963–7.

    Article  CAS  PubMed  Google Scholar 

  96. Salgado-Somoza A, Teijeira-Fernandez E, Rubio J, Couso E, Gonzalez-Juanatey JR, Eiras S. Coronary artery disease is associated with higher epicardial retinol-binding protein 4 (RBP4) and lower glucose transporter (GLUT) 4 levels in epicardial and subcutaneous adipose tissue. Clin Endocrinol. 2012;76:51–8.

    Article  CAS  Google Scholar 

  97. Silaghi A, Silaghi H, Scridon T, Pais R, Achard V. Glucocorticoid receptors in human epicardial adipose tissue: role of coronary status. J Endocrinol Investig. 2012;35:649–54.

    CAS  Google Scholar 

  98. Cappellano G, Uberti F, Caimmi PP, Pietronave S, Mary DA, Dianzani C, et al. Different expression and function of the endocannabinoid system in human epicardial adipose tissue in relation to heart disease. Can J Cardiol. 2013;29:499–509.

    Article  PubMed  Google Scholar 

  99. Teijeira-Fernandez E, Eiras S, Grigorian-Shamagian L, Fernandez A, Adrio B, Gonzalez-Juanatey JR. Epicardial adipose tissue expression of adiponectin is lower in patients with hypertension. J Hum Hypertens. 2008;22:856–63.

    Article  CAS  PubMed  Google Scholar 

  100. Kourliouros A, Karastergiou K, Nowell J, Gukop P, Tavakkoli Hosseini M, Valencia O, et al. Protective effect of epicardial adiponectin on atrial fibrillation following cardiac surgery. Eur J Cardiothorac Surg. 2011;39:228–32.

    Article  PubMed  Google Scholar 

  101. Suffee N, Moore-Morris T, Farahmand P, Rucker-Martin C, Dilanian G, Fradet M, et al. Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria. Proc Natl Acad Sci U S A. 2017;114:E771–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang Q, Xi W, Yin L, Wang J, Shen H, Gao Y, et al. Human epicardial adipose tissue cTGF expression is an independent risk factor for atrial fibrillation and highly associated with atrial fibrosis. Sci Rep. 2018;8:3585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang Q, Min J, Jia L, Xi W, Gao Y, Diao Z, et al. Human Epicardial adipose tissue activin a expression predicts occurrence of postoperative atrial fibrillation in patients receiving cardiac surgery. Heart Lung Circ. 2019;28:1697–705.

    Article  PubMed  Google Scholar 

  104. Couselo-Seijas M, Lopez-Canoa JN, Agra-Bermejo RM, Diaz-Rodriguez E, Fernandez AL, Martinez-Cereijo JM, et al. Cholinergic activity regulates the secretome of epicardial adipose tissue: association with atrial fibrillation. J Cell Physiol. 2019;234:10512–22.

    Article  CAS  PubMed  Google Scholar 

  105. Zangi L, Oliveira MS, Ye LY, Ma Q, Sultana N, Hadas Y, et al. Insulin-like growth factor 1 receptor-dependent pathway drives epicardial adipose tissue formation after myocardial injury. Circulation. 2017;135:59–72.

    Article  CAS  PubMed  Google Scholar 

  106. Agra RM, Teijeira-Fernandez E, Pascual-Figal D, Sanchez-Mas J, Fernandez-Trasancos A, Gonzalez-Juanatey JR, et al. Adiponectin and p53 mRNA in epicardial and subcutaneous fat from heart failure patients. Eur J Clin Investig. 2014;44:29–37.

    Article  CAS  Google Scholar 

  107. Perez-Belmonte LM, Moreno-Santos I, Gomez-Doblas JJ, Garcia-Pinilla JM, Morcillo-Hidalgo L, Garrido-Sanchez L, et al. Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure. Int J Med Sci. 2017;14:891–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Teijeira-Fernandez E, Eiras S, Grigorian-Shamagian L, Salgado-Somoza A, Martinez-Comendador JM, Gonzalez-Juanatey JR. Diabetic and nondiabetic patients express similar adipose tissue adiponectin and leptin levels. Int J Obes. 2010;34:1200–8.

    Article  CAS  Google Scholar 

  109. Gormez S, Demirkan A, Atalar F, Caynak B, Erdim R, Sozer V, et al. Adipose tissue gene expression of adiponectin, tumor necrosis factor-alpha and leptin in metabolic syndrome patients with coronary artery disease. Intern Med. 2011;50:805–10.

    Article  CAS  PubMed  Google Scholar 

  110. Castro RB, Longui CA, Faria CD, Silva TS, Richeti F, Rocha MN, et al. Tissue-specific adaptive levels of glucocorticoid receptor alpha mRNA and their relationship with insulin resistance. Genet Mol Res. 2012;11:3975–87.

    Article  CAS  PubMed  Google Scholar 

  111. Agra RM, Fernandez-Trasancos A, Sierra J, Gonzalez-Juanatey JR, Eiras S. Differential association of S100A9, an inflammatory marker, and p53, a cell cycle marker, expression with epicardial adipocyte size in patients with cardiovascular disease. Inflammation. 2014;37:1504–12.

    Article  CAS  PubMed  Google Scholar 

  112. Moreno-Santos I, Perez-Belmonte LM, Macias-Gonzalez M, Mataro MJ, Castellano D, Lopez-Garrido M, et al. Type 2 diabetes is associated with decreased PGC1alpha expression in epicardial adipose tissue of patients with coronary artery disease. J Transl Med. 2016;14:243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Liu Y, Fu W, Lu M, Huai S, Song Y, Wei Y. Role of miRNAs in epicardial adipose tissue in CAD patients with T2DM. Biomed Res Int. 2016;2016:1629236.

    PubMed  PubMed Central  Google Scholar 

  114. Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, et al. Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone. Diabetes Care. 2011;34:730–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Grosso AF, de Oliveira SF, Higuchi Mde L, Favarato D, Dallan LA, da Luz PL. Synergistic anti-inflammatory effect: simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome. Diabetol Metab Syndr. 2014;6:47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fiore D, Gianfrilli D, Giannetta E, Galea N, Panio G, di Dato C, et al. PDE5 inhibition ameliorates visceral adiposity targeting the miR-22/SIRT1 pathway: evidence from the CECSID trial. J Clin Endocrinol Metab. 2016;101:1525–34.

    Article  CAS  PubMed  Google Scholar 

  117. Iacobellis G, Mohseni M, Bianco SD, Banga PK. Liraglutide causes large and rapid epicardial fat reduction. Obesity (Silver Spring). 2017;25:311–6.

    Article  CAS  Google Scholar 

  118. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Iacobellis G, Camarena V, Sant DW, Wang G. Human epicardial fat expresses glucagon-like peptide 1 and 2 receptors genes. Horm Metab Res. 2017;49:625–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We apologize to colleagues whose works we were not able to cite here due to space limitations. The work on the EAT transcriptome in the Wang Lab is supported by the grant R01NS089525 from the National Institutes of Health.

Author information

Authors and Affiliations

  1. John P. Hussman Institute for Human Genomics, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA

    Vladimir Camarena & Tyler C. Huff

  2. Biomedical Informatics, Department of Biological Engineering, Utah State University, Salt Lake City, UT, USA

    David W. Sant

  3. John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA

    Gaofeng Wang

Authors
  1. Vladimir Camarena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David W. Sant
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tyler C. Huff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gaofeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gaofeng Wang .

Editor information

Editors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA

    Gianluca Iacobellis

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Camarena, V., Sant, D.W., Huff, T.C., Wang, G. (2020). Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue. In: Iacobellis, G. (eds) Epicardial Adipose Tissue. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-030-40570-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-40570-0_3

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-40569-4

  • Online ISBN: 978-3-030-40570-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation