Adipokine-cytokine profile of adipocytes of epicardial adipose tissue in ischemic heart disease complicated by visceral obesity

Introduction. To date, cardiovascular diseases (CVD) remain the main cause of disability and mortality in population. The majority of ectopic fat deposits demonstrated a reliable association with cardiometabolic risks and clinical manifestations of most CVD. The elucidation of the metabolic features of adipocytes of epicardial adipose tissue localized in the immediate vicinity of the lesion in ischemic heart disease (IHD) can have both theoretical and practical significance for pathophysiology and cardiology.

Aim. To study the adipokine-cytokine profile of epicardial adipocytes (EA) and subcutaneous adipose tissue (SCAT), blood serum in relation to the area of visceral adipose tissue (AVAT), biochemical and rhelinic characteristics of IHD patients.

Methods. 84 patients (70 men and 14 women) with IHD were examined. In the presence of visceral obesity (VO), patients were divided into two groups. In patients with VO, adipocyte EA and SCAT were sampled, followed by cultivation and evaluation of adipokine and proinflammatory activity. The parameters of carbohydrate and lipid metabolism, adipokine and proinflammatory status in blood serum were determined.

Results. It has been established that the adipokine-cytokine profile of the adipocytes EA and SCAT differ. Adipocytes of EA in IHD on the background of VO are characterized by an increase in IL-1, TNF-α, leptin-adiponectin ratio and a decrease in the protective factors: adiponectin and anti-inflammatory cytokine IL-10. While adipocytes of SCAT were characterized by a decrease in the concentration of the soluble receptor to leptin and a more pronounced leptin resistance, and the increase in inflammatory cytokines was compensated by an increase in the concentration of IL-10, the presence of VO was associated with multivessel coronary disease, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, adipokine imbalance, and markers of inflammation. Thus, the value of the area of VO determined higher values of leptin concentration, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower soluble receptor for leptin content.

The conclusion. Thus, in IHD with VO the state of adipocytes, EA is characterized as "metabolic inflammation" and may indicate the direct involvement of adipocytes in the pathogenesis of IHD due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

visceral obesity, epicardial adipose tissue, insulinresistance, inflammation, dyslipidemia, cardiovascular disease, adipokines

1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;380(9859):2095-2128. doi: 10.1016/s0140-6736(12)61728-0.

2. Roth GA, Forouzanfar MH, Moran AE, et al. Demographic and Epidemiologic Drivers of Global Cardiovascular Mortality. N Engl J Med. 2015;372(14):1333-1341. doi: 10.1056/NEJMoa1406656.

3. Lainscak M, Blue L, Clark AL, et al. Self-care management of heart failure: practical recommendations from the Patient Care Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2011;13(2):115-126. doi: 10.1093/eurjhf/hfq219.

4. Veilleux A, Cote JA, Blouin K, et al. Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes. AJP: Endocrinology and Metabolism. 2012;302(8):E941-E949. doi: 10.1152/ajpendo.00069.2011.

5. Hall JE, da Silva AA, do Carmo JM, et al. Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins. J Biol Chem. 2010;285(23):17271-17276. doi: 10.1074/jbc.R110.113175.

6. Bergman RN, Kim SP, Catalano KJ, et al. Why Visceral Fat is Bad: Mechanisms of the Metabolic Syndrome. Obesity. 2006;14(2S):16S-19S. doi: 10.1038/oby.2006.277.

7. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med. 2005;2(10):536-543. doi: 10.1038/ncpcardio0319.

8. Britton KA, Fox CS. Ectopic Fat Depots and Cardiovascular Disease. Circulation. 2011;124(24):e837-e841. doi: 10.1161/circulationaha.111.077602.

9. Sjostrom L. Сomputer-tomography based multicompartment body composition technique and anthropometric predictions of lean body mass, total and subcutaneous adipose tissue. Int J Obes. 1991;15: 19—30.

10. Carswell KA, Lee M-J, Fried SK. Culture of Isolated Human Adipocytes and Isolated Adipose Tissue. Methods Mol Biol. 2012;806:203-214. doi: 10.1007/978-1-61779-367-7_14.

11. Suga H, Matsumoto D, Inoue K, et al. Numerical Measurement of Viable and Nonviable Adipocytes and Other Cellular Components in Aspirated Fat Tissue. Plast Reconstr Surg. 2008;122(1):103-114. doi: 10.1097/PRS.0b013e31817742ed.

12. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419. doi: 10.1007/bf00280883.

13. Misra M, Miller KK, Almazan C, et al. Hormonal and Body Composition Predictors of Soluble Leptin Receptor, Leptin, and Free Leptin Index in Adolescent Girls with Anorexia Nervosa and Controls and Relation to Insulin Sensitivity. J Clin Endocr Metab. 2004;89(7):3486-3495. doi: 10.1210/jc.2003-032251.

14. Отт А.В., Чумакова Г.А., Веселовская Н.Г. Значение лептинорезистентности в развитии различных метаболических фенотипов ожирения // Российский кардиологический журнал. – 2016. - №4. – С. 4-18. [Ott AV, Chumakova GA, Veselovskaya NG. A Resistance to Leptin in Development of Different Obesity Phenotypes. Russian Journal of Cardiology. 2016;(4):14-18. (In Russ).] doi: 10.15829/1560-4071-2016-4-14-18.

15. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2008;30(7):850-856. doi: 10.1093/eurheartj/ehn573.

16. Jeong J-W, Jeong MH, Yun KH, et al. Echocardiographic Epicardial Fat Thickness and Coronary Artery Disease. Circ J. 2007;71(4):536-539. doi: 10.1253/circj.71.536.

17. Donoso MA, Muñoz-Calvo MT, Barrios V, et al. Increased Leptin/Adiponectin Ratio and Free Leptin Index Are Markers of Insulin Resistance in Obese Girls during Pubertal Development. Horm Res Paediatr. 2013;80(5):363-370. doi: 10.1159/000356046.

18. Libby. P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135.

19. Chia S. Intra-Arterial Tumor Necrosis Factor-alpha Impairs Endothelium-Dependent Vasodilatation and Stimulates Local Tissue Plasminogen Activator Release in Humans. Arterioscler Thromb Vasc Biol. 2003;23(4):695-701. doi: 10.1161/01.atv.0000065195.22904.fa.

20. Lima MMO, Pareja JC, Alegre SM, et al. Visceral fat resection in humans: Effect on insulin sensitivity, beta-cell function, adipokines, and inflammatory markers. Obesity. 2013;21(3):E182-E189. doi: 10.1002/oby.20030.