The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles

Journal of Physiology

Volumn 595, Issue 12, 2017, Pages 3907-3917

  Antonopoulos, Alexios S ^a   Antoniades, Charalambos ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

adipokines; cardiac biology; epicardial adipose tissue; myocardium; redox state

Indexed keywords

ADIPOCYTE; CALCIUM CELL LEVEL; CARDIAC MUSCLE CELL; CELL DIFFERENTIATION; CELL PROTECTION; CORONARY ARTERY ATHEROSCLEROSIS; EPICARDIAL FAT; HEART; HEART ELECTROPHYSIOLOGY; HEART FUNCTION; HEART MUSCLE CONTRACTILITY; HEART MUSCLE FIBROSIS; HEART MUSCLE METABOLISM; HEART PROTECTION; HUMAN; MOLECULAR INTERACTION; NONHUMAN; OXIDATION REDUCTION STATE; PARACRINE SIGNALING; PRIORITY JOURNAL; REVIEW; ADIPOSE TISSUE; ANIMAL; CARDIAC MUSCLE; CARDIOVASCULAR DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; PERICARDIUM; PHYSIOLOGY;

ADIPOSE TISSUE; ANIMALS; CARDIOVASCULAR DISEASES; HEART; HUMANS; MYOCARDIUM; MYOCYTES, CARDIAC; PERICARDIUM;

EID: 85015196638     PISSN: 00223751     EISSN: 14697793     Source Type: Journal    
DOI: 10.1113/JP273049     Document Type: Review

References (54)

1. Anan M, Uchihashi K, Aoki S, Matsunobu A, Ootani A, Node K & Toda S (2011). A promising culture model for analyzing the interaction between adipose tissue and cardiomyocytes. Endocrinology 152, 1599–1605.
2. Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM & Casadei B (2012). Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol 59, 60–70.
3. Antonopoulos AS, Margaritis M, Coutinho P, Digby J, Patel R, Psarros C, Ntusi N, Karamitsos TD, Lee R, De Silva R, Petrou M, Sayeed R, Demosthenous M, Bakogiannis C, Wordsworth PB, Tousoulis D, Neubauer S, Channon KM & Antoniades C (2014). Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol 34, 2151–2159.
4. Antonopoulos AS, Margaritis M, Coutinho P, Shirodaria C, Psarros C, Herdman L, Sanna F, De Silva R, Petrou M, Sayeed R, Krasopoulos G, Lee R, Digby J, Reilly S, Bakogiannis C, Tousoulis D, Kessler B, Casadei B, Channon KM & Antoniades C (2015). Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue. Diabetes 64, 2207–2219.
5. Antonopoulos AS, Margaritis M, Verheule S, Recalde A, Sanna F, Herdman L, Psarros C, Nasrallah H, Coutinho P, Akoumianakis I, Brewer AC, Sayeed R, Krasopoulos G, Petrou M, Tarun A, Tousoulis D, Shah AM, Casadei B, Channon KM & Antoniades C (2016a). Mutual regulation of epicardial adipose tissue and myocardial redox state by PPAR-γ/adiponectin signalling. Circ Res 118, 842–855.
6. Antonopoulos AS, Oikonomou EK, Antoniades C & Tousoulis D (2016b). From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. Obes Rev 17, 989–1000.
7. Blumensatt M, Greulich S, Herzfeld de Wiza D, Mueller H, Maxhera B, Rabelink MJ, Hoeben RC, Akhyari P, Al-Hasani H, Ruige JB & Ouwens DM (2013). Activin A impairs insulin action in cardiomyocytes via up-regulation of miR-143. Cardiovasc Res 100, 201–210.
8. Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, Loureiro M, Patricio M, Antunes M & Carvalho E (2016). Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes. Am J Physiol Endocrinol Metab 310, E550–E564.
9. Burke AP, Farb A, Tashko G & Virmani R (1998). Arrhythmogenic right ventricular cardiomyopathy and fatty replacement of the right ventricular myocardium: are they different diseases? Circulation 97, 1571–1580.
10. Chandalia M, Garg A, Vuitch F & Nizzi F (1995). Postmortem findings in congenital generalized lipodystrophy. J Clin Endocrinol Metab 80, 3077–3081.
11. Cheng VY, Dey D, Tamarappoo B, Nakazato R, Gransar H, Miranda-Peats R, Ramesh A, Wong ND, Shaw LJ, Slomka PJ & Berman DS (2010). Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovasc Imaging 3, 352–360.
12. Cherian S, Lopaschuk GD & Carvalho E (2012). Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. Am J Physiol Endocrinol Metab 303, E937–E949.
13. Chilukoti RK, Giese A, Malenke W, Homuth G, Bukowska A, Goette A, Felix SB, Kanaan J, Wollert HG, Evert K, Verheule S, Jais P, Hatem SN, Lendeckel U & Wolke C (2015). Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. Int J Cardiol 187, 604–613.
14. Chiou CW, Eble JN & Zipes DP (1997). Efferent vagal innervation of the canine atria and sinus and atrioventricular nodes. The third fat pad. Circulation 95, 2573–2584.
15. Dabbah S, Komarov H, Marmor A & Assy N (2014). Epicardial fat, rather than pericardial fat, is independently associated with diastolic filling in subjects without apparent heart disease. Nutr Metab Cardiovasc Dis 24, 877–882.
16. Ding J, Hsu FC, Harris TB, Liu Y, Kritchevsky SB, Szklo M, Ouyang P, Espeland MA, Lohman KK, Criqui MH, Allison M, Bluemke DA & Carr JJ (2009). The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 90, 499–504.
17. Forouzandeh F, Chang SM, Muhyieddeen K, Zaid RR, Trevino AR, Xu J, Nabi F & Mahmarian JJ (2013). Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone? Circ Cardiovasc Imaging 6, 58–66.
18. Gaborit B, Venteclef N, Ancel P, Pelloux V, Gariboldi V, Leprince P, Amour J, Hatem SN, Jouve E, Dutour A & Clement K (2015). Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovasc Res 108, 62–73.
19. Greulich S, de Wiza DH, Preilowski S, Ding Z, Mueller H, Langin D, Jaquet K, Ouwens DM & Eckel J (2011). Secretory products of guinea pig epicardial fat induce insulin resistance and impair primary adult rat cardiomyocyte function. J Cell Mol Med 15, 2399–2410.
20. Greulich S, Maxhera B, Vandenplas G, de Wiza DH, Smiris K, Mueller H, Heinrichs J, Blumensatt M, Cuvelier C, Akhyari P, Ruige JB, Ouwens DM & Eckel J (2012). Secretory products from epicardial adipose tissue of patients with type 2 diabetes mellitus induce cardiomyocyte dysfunction. Circulation 126, 2324–2334.
21. Hassan M, Said K, Rizk H, ElMogy F, Donya M, Houseni M & Yacoub M (2016). Segmental peri-coronary epicardial adipose tissue volume and coronary plaque characteristics. Eur Heart J Cardiovasc Imaging 17, 1169–1177.
22. Ishikawa Y, Ishii T, Asuwa N & Masuda S (1997). Absence of atherosclerosis evolution in the coronary arterial segment covered by myocardial tissue in cholesterol-fed rabbits. Virchows Arch 430, 163–171.
23. Jacobson JT, Hutchinson MD, Cooper JM, Woo YJ, Shandler RS & Callans DJ (2011). Tissue-specific variability in human epicardial impedance. J Cardiovasc Electrophysiol 22, 436–439.
24. Karastergiou K, Evans I, Ogston N, Miheisi N, Nair D, Kaski JC, Jahangiri M & Mohamed-Ali V (2010). Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells. Arterioscler Thromb Vasc Biol 30, 1340–1346.
25. Kocyigit D, Gurses KM, Yalcin MU, Turk G, Evranos B, Yorgun H, Sahiner ML, Kaya EB, Hazirolan T, Tokgozoglu L, Oto MA, Ozer N & Aytemir K (2015). Periatrial epicardial adipose tissue thickness is an independent predictor of atrial fibrillation recurrence after cryoballoon-based pulmonary vein isolation. J Cardiovasc Comput Tomogr 9, 295–302.
26. Kunita E, Yamamoto H, Kitagawa T, Ohashi N, Oka T, Utsunomiya H, Urabe Y, Tsushima H, Awai K, Budoff MJ & Kihara Y (2014). Prognostic value of coronary artery calcium and epicardial adipose tissue assessed by non-contrast cardiac computed tomography. Atherosclerosis 233, 447–453.
27. Lage R, Moscoso I, Fernandez-Trasancos A, Cebro M, Couselo M, Fandino-Vaquero R, Bravo SB, Sierra J, Gonzalez-Juanatey JR & Eiras S (2015). Differential behaviour of epicardial adipose tissue-secretomes with high and low orosomucoid levels from patients with cardiovascular disease in H9C2 cells. Mol Cell Endocrinol 416, 77–87.
28. Levelt E, Pavlides M, Banerjee R, Mahmod M, Kelly C, Sellwood J, Ariga R, Thomas S, Francis J, Rodgers C, Clarke W, Sabharwal N, Antoniades C, Schneider J, Robson M, Clarke K, Karamitsos T, Rider O & Neubauer S (2016). Ectopic and visceral fat deposition in lean and obese patients with type 2 diabetes. J Am Coll Cardiol 68, 53–63.
29. Lin YK, Chen YC, Chen JH, Chen SA & Chen YJ (2012). Adipocytes modulate the electrophysiology of atrial myocytes: implications in obesity-induced atrial fibrillation. Basic Res Cardiol 107, 293.
30. Mahabadi AA, Berg MH, Lehmann N, Kalsch H, Bauer M, Kara K, Dragano N, Moebus S, Jockel KH, Erbel R & Mohlenkamp S (2013). Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol 61, 1388–1395.
31. Mahabadi AA, Lehmann N, Kalsch H, Bauer M, Dykun I, Kara K, Moebus S, Jockel KH, Erbel R & Mohlenkamp S (2014). Association of epicardial adipose tissue and left atrial size on non-contrast CT with atrial fibrillation: the Heinz Nixdorf Recall Study. Eur Heart J Cardiovasc Imaging 15, 863–869.
32. Mahajan R, Lau DH, Brooks AG, Shipp NJ, Manavis J, Wood JP, Finnie JW, Samuel CS, Royce SG, Twomey DJ, Thanigaimani S, Kalman JM & Sanders P (2015). Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol 66, 1–11.
33. Marchington JM & Pond CM (1990). Site-specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. Int J Obes 14, 1013–1022.
34. Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P, Shirodaria C, Sayeed R, Petrou M, De Silva R, Jalilzadeh S, Demosthenous M, Bakogiannis C, Tousoulis D, Stefanadis C, Choudhury RP, Casadei B, Channon KM & Antoniades C (2013). Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation 127, 2209–2221.
35. Mazurek T, Kobylecka M, Zielenkiewicz M, Kurek A, Kochman J, Filipiak KJ, Mazurek K, Huczek Z, Krolicki L & Opolski G (2016). PET/CT evaluation of F-FDG uptake in pericoronary adipose tissue in patients with stable coronary artery disease: Independent predictor of atherosclerotic lesions' formation? J Nucl Cardiol, doi: 10.1007/s12350-015-0370-6.
36. Nakanishi K, Fukuda S, Tanaka A, Otsuka K, Jissho S, Taguchi H, Yoshikawa J & Shimada K (2014). Persistent epicardial adipose tissue accumulation is associated with coronary plaque vulnerability and future acute coronary syndrome in non-obese subjects with coronary artery disease. Atherosclerosis 237, 353–360.
37. Nakanishi K, Fukuda S, Tanaka A, Otsuka K, Sakamoto M, Taguchi H, Yoshikawa J, Shimada K & Yoshiyama M (2012). Peri-atrial epicardial adipose tissue is associated with new-onset nonvalvular atrial fibrillation. Circ J 76, 2748–2754.
38. Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U & Casadei B (2011). Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation 124, 1107–1117.
39. Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, Karas J, Optican R, Bahouth SW, Garrett E, Wolf RY, Carter RA, Robbins T, Wolford D & Samaha J (2009). Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. J Clin Endocrinol Metab 94, 3611–3615.
40. Salgado-Somoza A, Teijeira-Fernandez E, Fernandez AL, Gonzalez-Juanatey JR & Eiras S (2010). Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress. Am J Physiol Heart Circ Physiol 299, H202–H209.
41. Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S & Sata M (2013). Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 33, 1077–1084.
42. Stojanovska J, Kazerooni EA, Sinno M, Gross BH, Watcharotone K, Patel S, Jacobson JA & Oral H (2015). Increased epicardial fat is independently associated with the presence and chronicity of atrial fibrillation and radiofrequency ablation outcome. Eur Radiol 25, 2298–2309.
43. Suffee N, Moris TM, Dilanian G, Farahmand P, Rucker-Martin C, Dugail I, Pucéat M & Hatem S (2016). Epicardial progenitors are source of adipocyte in human atria. Arch Cardiovasc Dis Suppl 8, 255.
44. Tamarappoo B, Dey D, Shmilovich H, Nakazato R, Gransar H, Cheng VY, Friedman JD, Hayes SW, Thomson LE, Slomka PJ, Rozanski A & Berman DS (2010). Increased pericardial fat volume measured from noncontrast CT predicts myocardial ischemia by SPECT. JACC Cardiovasc Imaging 3, 1104–1112.
45. Uchida Y, Uchida Y, Shimoyama E, Hiruta N, Kishimoto T & Watanabe S (2016). Pericoronary adipose tissue as storage and supply site for oxidized low-density lipoprotein in human coronary plaques. PLoS One 11, e0150862.
46. Venteclef N, Guglielmi V, Balse E, Gaborit B, Cotillard A, Atassi F, Amour J, Leprince P, Dutour A, Clement K & Hatem SN (2015). Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J 36, 795–805.
47. Verheule S, Tuyls E, Gharaviri A, Hulsmans S, van Hunnik A, Kuiper M, Serroyen J, Zeemering S, Kuijpers NH & Schotten U (2013). Loss of continuity in the thin epicardial layer because of endomysial fibrosis increases the complexity of atrial fibrillatory conduction. Circ Arrhythm Electrophysiol 6, 202–211.
48. Wang CP, Hsu HL, Hung WC, Yu TH, Chen YH, Chiu CA, Lu LF, Chung FM, Shin SJ & Lee YJ (2009a). Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis. Clin Endocrinol (Oxf) 70, 876–882.
49. Wang Y, Tao L, Yuan Y, Lau WB, Li R, Lopez BL, Christopher TA, Tian R & Ma XL (2009b). Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action. Am J Physiol Endocrinol Metab 297, E384–E391.
50. Woodward L, Akoumianakis I & Antoniades C (2016). Unravelling the adiponectin paradox: novel roles of adiponectin in the regulation of cardiovascular disease. Br J Pharmacol, DOI: 10.1111/bph.13619.
51. Yamaguchi Y, Cavallero S, Patterson M, Shen H, Xu J, Kumar SR & Sucov HM (2015). Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation. Proc Natl Acad Sci U S A 112, 2070–2075.
52. Yorgun H, Canpolat U, Aytemir K, Hazirolan T, Sahiner L, Kaya EB, Kabakci G, Tokgozoglu L, Ozer N & Oto A (2015). Association of epicardial and peri-atrial adiposity with the presence and severity of non-valvular atrial fibrillation. Int J Cardiovasc Imaging 31, 649–657.
53. Zangi L, Oliveira MS, Ye LY, Ma Q, Sultana N, Hadas Y, Chepurko E, Später D, Zhou B, Chew WL, Ebina W, Abrial M, Wang Q-D, Pu WT & Chien KR (2017). An IGF1R-dependent pathway drives epicardial adipose tissue formation after myocardial injury. Circulation 135, 59–72.
54. Zhu W, Zhang H, Guo L & Hong K (2015). Relationship between epicardial adipose tissue volume and atrial fibrillation: A systematic review and meta-analysis. Herz 41, 421–427.