Периваскулярная жировая ткань: роль в патогенезе ожирения, сахарного диабета 2 типа и сердечно-сосудистой патологии

Периваскулярная жировая ткань – часть сосудистой стенки, регулирующая эндоваскулярный гомеостаз, работу эндотелия и гладкомышечной мускулатуры. В норме периваскулярная ткань оказывает вазодилататорный и протективный эффекты, однако при ожирении, атеросклерозе и сахарном диабете 2 типа ткань претерпевает структурные и функциональные изменения. Накопленные данные свидетельствуют о возможной ключевой роли периваскулярной жировой ткани в патогенезе данных заболеваний. Показано, что периваскулярная ткань – независимый фактор сердечно-сосудистого риска даже при отсутствии висцерального ожирения. Основные механизмы включают локальное медленно прогрессирующее воспаление, оксидативный стресс, активацию тканевой ренин-ангиотензин-альдостероновой системы, паракринные и метаболические изменения. Свойства периваскулярной ткани зависят от типа адипоцитов. Традиционно бурый жир расценивается как метаболически благоприятный, однако бурая периваскулярная ткань при определенных условиях может способствовать развитию дислипидемии. Целью данного обзора является обсуждение данных современной литературы, отражающих особенности периваскулярной жировой ткани, изменения её активности, секреторного и генетического профиля при социально значимых заболеваниях, молекулярные механизмы функционирования. Кроме того, обсуждаются перспективы воздействия на метаболические пути и гены периваскулярной жировой ткани для эффективной профилактики ожирения, сахарного диабета 2 типа и сердечно-сосудистой патологии.

периваскулярная жировая ткань, ожирение, сахарный диабет 2 типа, аденозинмонофосфат-активируемая протеинкиназа

1. Miao C-Y, Li Z-Y. The role of perivascular adipose tissue in vascular smooth muscle cell growth. British Journal of Pharmacology. 2012;165(3):643-58. doi: 10.1111/j.1476-5381.2011.01404.x

2. Soltis EE, Cassis LA. Influence of Perivascular Adipose Tissue on Rat Aortic Smooth Muscle Responsiveness. Clinical and Experimental Hypertension Part A: Theory and Practice. 2009;13(2):277-96. doi: 10.3109/10641969109042063

3. Lohn M. Periadventitial fat releases a vascular relaxing factor. The FASEB Journal. 2002;16(9):1057-63. doi: 10.1096/fj.02-0024com

4. Almabrouk TAM, Ewart MA, Salt IP, Kennedy S. Perivascular fat, AMP-activated protein kinase and vascular diseases. British Journal of Pharmacology. 2014;171(3):595-617. doi: 10.1111/bph.12479

5. Barandier C. Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. AJP: Heart and Circulatory Physiology. 2005;289(5):H1807-H13. doi: 10.1152/ajpheart.01259.2004

6. Souza DSR, Johansson B, Bojö L, Karlsson R, Geijer H, Filbey D, et al. Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery: Results of a randomized longitudinal trial. The Journal of Thoracic and Cardiovascular Surgery. 2006;132(2):373-8.e5. doi: 10.1016/j.jtcvs.2006.04.002

7. Wang P, Xu TY, Guan YF, Su DF, Fan GR, Miao CY. Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovascular Research. 2008;81(2):370-80. doi: 10.1093/cvr/cvn288

8. Takaoka M, Nagata D, Kihara S, Shimomura I, Kimura Y, Tabata Y, et al. Periadventitial Adipose Tissue Plays a Critical Role in Vascular Remodeling. Circulation Research. 2009;105(9):906-11. doi: 10.1161/circresaha.109.199653

9. Frontini A, Cinti S. Distribution and Development of Brown Adipocytes in the Murine and Human Adipose Organ. Cell Metabolism. 2010;11(4):253-6. doi: 10.1016/j.cmet.2010.03.004

10. Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory Phenotype of Perivascular Adipocytes: Influence of High-Fat Feeding. Circulation Research. 2009;104(4):541-9. doi: 10.1161/circresaha.108.182998

11. Ruan CC, Zhu DL, Chen QZ, Chen J, Guo SJ, Li XD, et al. Perivascular Adipose Tissue-Derived Complement 3 Is Required for Adventitial Fibroblast Functions and Adventitial Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30(12):2568-74. doi: 10.1161/atvbaha.110.215525

12. Meijer RI, Serne EH, Smulders YM, van Hinsbergh VWM, Yudkin JS, Eringa EC. Perivascular Adipose Tissue and Its Role in Type 2 Diabetes and Cardiovascular Disease. Current Diabetes Reports. 2011;11(3):211-7. doi: 10.1007/s11892-011-0186-y

13. Rajsheker S, Manka D, Blomkalns AL, Chatterjee TK, Stoll LL, Weintraub NL. Crosstalk between perivascular adipose tissue and blood vessels. Current Opinion in Pharmacology. 2010;10(2):191-6. doi: 10.1016/j.coph.2009.11.005 14. Mattu HS, Randeva HS. Role of adipokines in cardiovascular disease. Journal of Endocrinology. 2012;216(1):T17-T36. doi: 10.1530/joe-12-0232

14. Rodríguez A, Fortuño A, Gómez-Ambrosi J, Zalba G, Díez J, Frühbeck G. The Inhibitory Effect of Leptin on Angiotensin II-Induced Vasoconstriction in Vascular Smooth Muscle Cells Is Mediated via a Nitric Oxide-Dependent Mechanism. Endocrinology. 2007;148(1):324-31. doi: 10.1210/en.2006-0940

15. Galvez B. Perivascular Adipose Tissue and Mesenteric Vascular Function in Spontaneously Hypertensive Rats. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26(6):1297-302. doi: 10.1161/01.ATV.0000220381.40739.dd

16. Thalmann S, Meier C. Local adipose tissue depots as cardiovascular risk factors. Cardiovascular Research. 2007;75(4):690-701. doi: 10.1016/j.cardiores.2007.03.008

17. 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. International Journal of Obesity. 2007;32(2):268-74. doi: 10.1038/sj.ijo.0803726

18. G. Spiroglou S, G. Kostopoulos C, N. Varakis J, H. Papadaki H. Adipokines in Periaortic and Epicardial Adipose Tissue: Differential Expression and Relation to Atherosclerosis. Journal of Atherosclerosis and Thrombosis. 2010;17(2):115-30. doi: 10.5551/jat.1735

19. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al. Local Inflammation and Hypoxia Abolish the Protective Anticontractile Properties of Perivascular Fat in Obese Patients. Circulation. 2009;119(12):1661- 70. doi: 10.1161/circulationaha.108.821181

20. Lynch FM, Withers SB, Yao Z, Werner ME, Edwards G, Weston AH, et al. Perivascular adipose tissue-derived adiponectin activates BKCa channels to induce anticontractile responses. AJP: Heart and Circulatory Physiology. 2013;304(6):H786-H95. doi: 10.1152/ajpheart.00697.2012

21. Zhu W, Cheng Kenneth KY, Vanhoutte Paul M, Lam Karen SL, Xu A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clinical Science. 2008;114(5):361-74. doi: 10.1042/cs20070347

22. Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice. Circulation Journal. 2010;74(7):1479-87. doi: 10.1253/circj.CJ-09-0661

23. Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL. Endothelial Nitric Oxide Synthase Uncoupling and Perivascular Adipose Oxidative Stress and Inflammation Contribute to Vascular Dysfunction in a Rodent Model of Metabolic Syndrome. Hypertension. 2009;54(6):1384-92. doi: 10.1161/hypertensionaha.109.138305

24. Meijer RI, Bakker W, Alta CLAF, Sipkema P, Yudkin JS, Viollet B, et al. Perivascular Adipose Tissue Control of Insulin-Induced Vasoreactivity in Muscle Is Impaired in db/db Mice. Diabetes. 2012;62(2):590-8. doi: 10.2337/db11-1603

25. Lobato NS, Neves KB, Filgueira FP, Fortes ZB, Carvalho MHC, Webb RC, et al. The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway. Life Sciences. 2012;91(13-14):600-6. doi: 10.1016/j.lfs.2012.04.013

26. Szasz T, Bomfim Gf, Webb. The influence of perivascular adipose tissue on vascular homeostasis. Vascular Health and Risk Management. 2013:105. doi: 10.2147/vhrm.s33760

27. Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochemical and Biophysical Research Communications. 2010;393(4):668-72. doi: 10.1016/j.bbrc.2010.02.053

28. Gao Y, Takemori K, Su L, An W, Lu C, Sharma A, et al. Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovascular Research. 2006;71(2):363-73. doi: 10.1016/j.cardiores.2006.03.013

29. Wójcicka G, Jamroz-Wiśniewska A, Atanasova P, Chaldakov GN, Chylińska-Kula B, Bełtowski J. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacological Research. 2011;63(1):68-76. doi: 10.1016/j.phrs.2010.10.011

30. Lee YC, Chang HH, Chiang CL, Liu CH, Yeh JI, Chen MF, et al. Role of Perivascular Adipose Tissue-Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension. Circulation. 2011;124(10):1160-71. doi: 10.1161/circulationaha.111.027375

31. Lu C, Su L-Y, Lee RMKW, Gao Y-J. Alterations in perivascular adipose tissue structure and function in hypertension. European Journal of Pharmacology. 2011;656(1-3):68-73. doi: 10.1016/j.ejphar.2011.01.023

32. Rittig K, Dolderer JH, Balletshofer B, Machann J, Schick F, Meile T, et al. The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells. Diabetologia. 2012;55(5):1514-25. doi: 10.1007/s00125-012-2481-9

33. Mazurek T. Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators. Circulation. 2003;108(20):2460-6. doi: 10.1161/01.cir.0000099542.57313.c5

34. Rittig K, Staib K, Machann J, Böttcher M, Peter A, Schick F, et al. Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction. Diabetologia. 2008;51(11):2093-9. doi: 10.1007/s00125-008-1128-3

35. Goodpaster BH, Thaete FL, Kelley DE. Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr. 2000; 71(4):885-92.

36. Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, et al. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia. 2009;52(5):752-64. doi: 10.1007/s00125-009-1313-z

37. Eringa EC, Bakker W, Smulders YM, Serné EH, Yudkin JS, Stehouwer CDA. Regulation of Vascular Function and Insulin Sensitivity by Adipose Tissue: Focus on Perivascular Adipose Tissue. Microcirculation. 2007;14(4-5):389-402. doi: 10.1080/10739680701303584

38. Fernández-Alfonso MS, Gil-Ortega M, García-Prieto CF, Aranguez I, Ruiz-Gayo M, Somoza B. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity. International Journal of Endocrinology. 2013;2013:1-8. doi: 10.1155/2013/402053

39. Hayden MR, Sowers KM, Pulakat L, Joginpally T, Krueger B, Whaley-Connell A, et al. Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus. Cardiorenal Medicine. 2011;1(3):193-210. doi: 10.1159/000329926

40. Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. AJP: Heart and Circulatory Physiology. 2011;301(4):H1425-H37. doi: 10.1152/ajpheart.00376.2011

41. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. Effects of Bariatric Surgery on Human Small Artery Function. Journal of the American College of Cardiology. 2013;62(2):128-35. doi: 10.1016/j.jacc.2013.04.027

42. Britton KA, Pedley A, Massaro JM, Corsini EM, Murabito JM, Hoffmann U, et al. Prevalence, Distribution, and Risk Factor Correlates of High Thoracic Periaortic Fat in the Framingham Heart Study. Journal of the American Heart Association. 2012;1(6):e004200-e. doi: 10.1161/jaha.112.004200

43. Henrichot E. Production of Chemokines by Perivascular Adipose Tissue: A Role in the Pathogenesis of Atherosclerosis? Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25(12):2594-9. doi: 10.1161/01.atv.0000188508.40052.35

44. Öhman MK, Luo W, Wang H, Guo C, Abdallah W, Russo HM, et al. Perivascular visceral adipose tissue induces atherosclerosis in apolipoprotein E deficient mice. Atherosclerosis. 2011;219(1):33-9. doi: 10.1016/j.atherosclerosis.2011.07.012

45. Shyu K-G, Lien L-M, Wang B-W, Kuan P, Chang H. Resistin contributes to neointimal formation via oxidative stress after vascular injury. Clinical Science. 2011;120(3):121-9. doi: 10.1042/cs20100226

46. Briones AM, Nguyen Dinh Cat A, Callera GE, Yogi A, Burger D, He Y, et al. Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways: Implications in Diabetes Mellitus-Associated Obesity and Vascular Dysfunction. Hypertension. 2012;59(5):1069-78. doi: 10.1161/hypertensionaha.111.190223

47. Liao D, Arnett DK, Tyroler HA, Riley WA, Chambless LE, Szklo M, et al. Arterial Stiffness and the Development of Hypertension : The ARIC Study. Hypertension. 1999;34(2):201-6. doi: 10.1161/01.hyp.34.2.201

48. Verhagen SN, Buijsrogge MP, Vink A, van Herwerden LA, van der Graaf Y, Visseren FLJ. Secretion of adipocytokines by perivascular adipose tissue near stenotic and non-stenotic coronary artery segments in patients undergoing CABG. Atherosclerosis. 2014;233(1):242-7. doi: 10.1016/j.atherosclerosis.2013.12.005

49. Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, et al. Loss of Perivascular Adipose Tissue on Peroxisome Proliferator-Activated Receptor- Deletion in Smooth Muscle Cells Impairs Intravascular Thermoregulation and Enhances Atherosclerosis. Circulation. 2012;126(9):1067-78. doi: 10.1161/circulationaha.112.104489

50. Dong M, Yang X, Lim S, Cao Z, Honek J, Lu H, et al. Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis. Cell Metabolism. 2013;18(1):118-29. doi: 10.1016/j.cmet.2013.06.00