Статья
Экспрессия гена адипонектина в эпикардиальной и подкожной жировой ткани при ишемической болезни сердца
Цель Определить экспрессию гена адипонектина (ADIPOQ) и содержание высокомолекулярной формы адипонектина (ВМАН) в эпикардиальной (ЭЖТ) и подкожной жировой ткани (ПЖТ) у пациентов с ишемической болезнью сердца (ИБС).Материал и методы Были исследованы парные образцы ЭЖТ и ПЖТ, сыворотки крови 74 пациентов с ИБС, перенесших операцию коронарного шунтирования, и 16 лиц без ИБС (группа сравнения). Уровень матричной РНК (мРНК) оценивали с помощью полимеразной цепной реакции в реальном времени. Для оценки уровня ВМАН в ЭЖТ и ПЖТ использовался метод вестерн-блоттинг. Концентрацию адипонектина в сыворотке крови измеряли методом иммуноферментного анализа. Всем пациентам проводили эхокардиографическое исследование с целью определения толщины ЭЖТ и коронароангиографию для определения тяжести коронарного атеросклероза.Результаты Концентрация адипонектина в сыворотке крови была ниже у пациентов с ИБС, чем в группе сравнения (p<0,001). Уровень мРНК гена ADIPOQ, а также ВМАН в ПЖТ был ниже у пациентов с ИБС, чем в группе сравнения (р=0,020 и p=0,003 соответственно). Уровень ВМАН в ЭЖТ был ниже при толщине ЭЖТ более 8 мм по сравнению с этим показателем у пациентов с ИБС и толщиной ЭЖТ ≤8 мм (p=0,034).Заключение Снижение концентрации антиатерогенного адипонектина сыворотки крови и снижение экспрессии гена ADIPOQ в ПЖТ (мРНК, ВМАН) ассоциированы с ИБС.
1. W-hite U, Ravussin E. Dynamics of adipose tissue turnover in human metabolic health and disease. Diabetologia. 2019;62(1):17–23. DOI: 10.1007/s00125-018-4732-x
2. Iacobellis G. Epicardial fat: a new cardiovascular therapeutic target. Current Opinion in Pharmacology. 2016;27:13–8. DOI: 10.1016/j.coph.2016.01.004
3. Iwasaki K, Urabe N, Kitagawa A, Nagao T. The association of epicardial fat volume with coronary characteristics and clinical outcome. The International Journal of Cardiovascular Imaging. 2018;34(2):301–9. DOI: 10.1007/s10554-017-1227-7
4. Nagy E, Jermendy AL, Merkely B, Maurovich-Horvat P. Clinical importance of epicardial adipose tissue. Archives of Medical Science. 2017;13(4):864–74. DOI: 10.5114/aoms.2016.63259
5. Chistiakov DA, Grechko AV, Myasoedova VA, Melnichenko AA, Orekhov AN. Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology. Atherosclerosis. 2017;263:361–8. DOI: 10.1016/j.atherosclerosis.2017.06.017
6. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular Medicine. 2005;2(10):536–43. DOI: 10.1038/ncpcardio0319
7. Gaborit B, Sengenes C, Ancel P, Jacquier A, Dutour A. Role of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat? Comprehensive Physiology. 2017;7(3):1051–82. DOI: 10.1002/cphy.c160034
8. Douglass E, Greif S, Frishman WH. Epicardial Fat: Pathophysiology and Clinical Significance. Cardiology in Review. 2017;25(5):230–5. DOI: 10.1097/CRD.0000000000000153
9. Karbowska J, Kochan Z. Role of adiponectin in the regulation of carbohydrate and lipid metabolism. Journal of Physiology and Pharmacology. 2006;57(Suppl 6):103–13. PMID: 17228091
10. Villarreal-Molina MT, Antuna-Puente B. Adiponectin: Anti-inflammatory and cardioprotective effects. Biochimie. 2012;94(10):2143–9. DOI: 10.1016/j.biochi.2012.06.030
11. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. Journal of the American Society of Nephrology. 2002;13(1):134–41. PMID: 11752030
12. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M et al. Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice. Circulation. 2002;106(22):2767–70. DOI: 10.1161/01.CIR.0000042707.50032.19
13. Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin Levels and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA. 2009;302(2):179–88. DOI: 10.1001/jama.2009.976
14. Rutkowski JM, Scherer PE. Isolation and Quantitation of Adiponectin Higher Order Complexes. Methods in Enzymology. 2014;537:243–59. DOI: 10.1016/B978-0-12-411619-1.00013-6
15. Belyaeva O.D., Brovin D.L., Berezina A.V., Karonova T.L., Chubenko E.A., Berkovich O.A., et al. Total and high-molecular weight adiponectin level in hypertensive women with abdominal obesity. Arterial Hypertension. 2014;20(5):442–9.
16. Pischon T, Hu FB, Girman CJ, Rifai N, Manson JE, Rexrode KM et al. Plasma total and high molecular weight adiponectin levels and risk of coronary heart disease in women. Atherosclerosis. 2011;219(1):322–9. DOI: 10.1016/j.atherosclerosis.2011.07.011
17. Du Y, Ji Q, Cai L, Huang F, Lai Y, Liu Y et al. Association between omentin-1 expression in human epicardial adipose tissue and coronary atherosclerosis. Cardiovascular Diabetology. 2016;15(1):90. DOI: 10.1186/s12933-016-0406-5
18. Gormez S, Demirkan A, Atalar F, Caynak B, Erdim R, Sozer V et al. Adipose Tissue Gene Expression of Adiponectin, Tumor Necrosis Factor-α and Leptin in Metabolic Syndrome Patients with Coronary Artery Disease. Internal Medicine. 2011;50(8):805–10. DOI: 10.2169/internalmedicine.50.4753
19. 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(6):251–5. DOI: 10.1016/j.cyto.2004.11.002
20. Norlén A, Alvén J, Molnar D, Enqvist O, Norrlund RR, Brandberg J et al. Automatic pericardium segmentation and quantification of epicardial fat from computed tomography angiography. Journal of Medical Imaging. 2016;3(3):034003. DOI: 10.1117/1.JMI.3.3.034003
21. Kuznetsova T.Yu., Chumakova G.A., Druzhilov M.A., Veselovskaya N.G. Clinical application of quantitative echocardiography assessment of epicardial fat tissue in obesity. Russian Journal of Cardiology. 2017;22(4):81–7.. DOI: 10.15829/1560-4071-2017-4-81-87
22. Bokeria L. A., Aronov D. M. Russian clinical guidelines Coronary artery bypass grafting in patients with ischemic heart disease: rehabilitation and secondary prevention. CardioSomatics. 2016;7(3–4):5–71.
23. Montalescot G, Sechtem W, Achenbach S, Andreotti F, Arden C, Budaj A et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. European Heart Journal. 2013;34(38):2949–3003. DOI: 10.1093/eurheartj/eht296
24. Miroshnikova V.V., Panteleeva A.A., Bazhenova E.A., Demina E.P., Usenko T.S., Nikolaev M.A. et al. Regulation of ABCA1 and ABCG1 gene expression in the intraabdominal adipose tissue. Biomedical Chemistry. 2016;62 (3):283–9.. DOI: 10.18097/PBMC20166203283
25. Ogorodnikova AD, Wassertheil-Smoller S, Mancuso P, Sowers MR, Rajpathak SN, Allison MA et al. High-Molecular-Weight Adiponectin and Incident Ischemic Stroke in Postmenopausal Women: A Women’s Health Initiative Study. Stroke. 2010;41(7):1376–81. DOI: 10.1161/STROKEAHA.109.576546
26. Brovin D.L., Belyaeva O.D., Pchelina S.N., Berezina A.V., Karonova T.L., Bazhenova E.A. et al. Common Carotid Intima–Media Thickness, Levels of Total and High-Molecular Weight Adiponectin in Women with Abdominal Obesity. Kardiologiia. 2018;58(6):29–36.. DOI: 10.18087/cardio.2018.6.10122
27. Kizer JR, Benkeser D, Arnold AM, Djousse L, Zieman SJ, Mukamal KJ et al. Total and High-Molecular-Weight Adiponectin and Risk of Coronary Heart Disease and Ischemic Stroke in Older Adults. The Journal of Clinical Endocrinology & Metabolism. 2013;98(1):255–63. DOI: 10.1210/jc.2012-2103
28. Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domienik-Karlowicz J et al. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabetology & Metabolic Syndrome. 2017;9(1):95. DOI: 10.1186/s13098-017-0293-2
29. Sadashiv, Tiwari S, Paul BN, Kumar S, Chandra A, Dhananjai S et al. Adiponectin mRNA in adipose tissue and its association with metabolic risk factors in postmenopausal obese women. Hormones. 2013;12(1):119–27. DOI: 10.1007/BF03401293
30. Razgildina N.D., Brovin D.L., Pobozheva I.A., Panteleeva A.A., Miroshnikova V.V., Belyaeva O.D. et al. Adiponectine gene expression in subcutaneous and intra-abdominal adipose tissue in women with varying degrees of obesity. Tsitologiya. 2018;60(7):531–5.. DOI: 10.31116/tsitol.2018.07.08
31. Bambace C, Sepe A, Zoico E, Telesca M, Olioso D, Venturi S et al. Inflammatory profile in subcutaneous and epicardial adipose tissue in men with and without diabetes. Heart and Vessels. 2014;29(1):42–8. DOI: 10.1007/s00380-012-0315-9
32. Eiras S, Teijeira-Fernández 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(2):174–80. DOI: 10.1016/j.cyto.2008.05.006
33. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Molecular and Cellular Endocrinology. 2004;219(1–2):9–15. DOI: 10.1016/j.mce.2004.03.002
34. Iacobellis G, Tiziana di Gioia C, Cotesta D, Petramala L, Travaglini C, De Santis V et al. Epicardial Adipose Tissue Adiponectin Expression is Related to Intracoronary Adiponectin Levels. Hormone and Metabolic Research. 2009;41(03):227–31. DOI: 10.1055/s-0028-1100412
35. Fuster JJ, Ouchi N, Gokce N, Walsh K. Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease. Circulation Research. 2016;118(11):1786–807. DOI: 10.1161/CIRCRESAHA.115.306885
36. Tachibana M, Miyoshi T, Osawa K, Toh N, Oe H, Nakamura K et al. Measurement of epicardial fat thickness by transthoracic echocardiography for predicting high-risk coronary artery plaques. Heart and Vessels. 2016;31(11):1758–66. DOI: 10.1007/s00380-016-0802-5
37. Fuller B, Garland J, Anne S, Beh R, McNevin D, Tse R. Increased Epicardial Fat Thickness in Sudden Death From Stable Coronary Artery Atherosclerosis: The American Journal of Forensic Medicine and Pathology. 2017;38(2):162–6. DOI: 10.1097/PAF.0000000000000310
38. Ansari MA, Mohebati M, Poursadegh F, Foroughian M, Sepehri Shamloo A. Is echocardiographic epicardial fat thickness increased in patients with coronary artery disease? A systematic review and meta-analysis. Electronic Physician. 2018;10(9):7249–58. DOI: 10.19082/7249
39. Eroglu S, Sade LE, Yildirir A, Bal U, Ozbicer S, Ozgul AS et al. Epicardial adipose tissue thickness by echocardiography is a marker for the presence and severity of coronary artery disease. Nutrition, Metabolism and Cardiovascular Diseases. 2009;19(3):211–7. DOI: 10.1016/j.numecd.2008.05.002
40. Chu C-Y, Lee W-H, Hsu P-C, Lee M-K, Lee H-H, Chiu C-A et al. Association of Increased Epicardial Adipose Tissue Thickness with Adverse Cardiovascular Outcomes in Patients with Atrial Fibrillation: Medicine. 2016;95(11):e2874. DOI: 10.1097/MD.0000000000002874
41. Lu C, Jia H, Wang Z. Association between epicardial adipose tissue and adverse outcomes in coronary heart disease patients with percutaneous coronary intervention. Bioscience Reports. 2019;39(5):BSR20182278. DOI: 10.1042/BSR20182278
42. Sade LE, Eroglu S, Bozbaş H, Özbiçer S, Hayran M, Haberal A et al. Relation between epicardial fat thickness and coronary flow reserve in women with chest pain and angiographically normal coronary arteries. Atherosclerosis. 2009;204(2):580–5. DOI: 10.1016/j.atherosclerosis.2008.09.038
43. Liu M, Liu F. Regulation of adiponectin multimerization, signaling and function. Best Practice & Research Clinical Endocrinology & Metabolism. 2014;28(1):25–31. DOI: 10.1016/j.beem.2013.06.003
44. Toczylowski K, Hirnle T, Harasiuk D, Zabielski P, Lewczuk A, Dmitruk I et al. Plasma concentration and expression of adipokines in epicardial and subcutaneous adipose tissue are associated with impaired left ventricular filling pattern. Journal of Translational Medicine. 2019;17(1):310. DOI: 10.1186/s12967-019-2060-7