ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet201545-13ometendo-7584Research ArticleОбзор литературыReviewПериваскулярная жировая ткань: роль в патогенезе ожирения, сахарного диабета 2 типа и сердечно-сосудистой патологииPerivascular adipose tissue: role in the pathogenesis of obesity, type 2 diabetes mellitus and cardiovascular pathology.РоманцоваТатьяна ИвановнаRomantsovaTat'yana Ivanovna

д.м.н., профессор кафедры эндокринологии Первого МГМУ им. И.М. Сеченова

MD Ph.D., professor of endocrinology

romantsovatatiana@rambler.ruОвсянниковаАриадна ВасильевнаOvsyannikovnaAriadna Vasil'evna

студентка 6 курса ЦИОП«Медицина будущего» Первого МГМУ им. И.М. Сеченова

student

ariadna.ovsiannikova@gmail.comПервый МГМУ им. И.М. СеченоваРоссияI. M. Sechenov's First Moscow State Medical UniversityRussian Federation201521092015124513Copyright © Романцова Т.И., Овсянникова А.В., 20152015Романцова Т.И., Овсянникова А.В.Romantsova T.I., Ovsyannikovna A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/7584

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.

Perivascular adipose tissue is a part of blood vessel wall, regulating endovascular homeostasis, endothelial and smooth muscle cells functioning. Under physiological conditions, perivascular tissue provides beneficial anticontractile effect, though undergoes structural and functional changes in obesity, atherosclerosis and diabetes mellitus type2.Collected data suggest the possible key role of perivascular adipose tissue in the pathogenesis of these diseases. Perivascular tissue has been determined as an independent cardiovascular risk factor, regardless of visceral obesity. General mechanisms include a local low-grade inflammation, oxidative stress, tissue renin-angiotensin-aldosterone system activation, paracrine and metabolic alterations. Properties of perivascular adipose tissue depend on the certain type of adipocytes it contains. Brown adipocytes are well known for their metabolic preferences, however it has been shown recently that brown perivascular tissue can contribute to dyslipidemia under some conditions.  The aim of this review is to discuss the current literature understanding of perivascular adipose tissue specifics, changes in its activity, secretory and genetic profilein a course of the most common non-infectious diseases development, as well as molecular mechanisms of its functioning. We also discuss perspectives of target interventions using metabolic pathways and genes of perivascular tissue, for the effective prevention of obesity, diabetes mellitus type2 and cardiovascular diseases.

периваскулярная жировая тканьожирениесахарный диабет 2 типааденозинмонофосфат-активируемая протеинкиназаperivascular adipose tissueobesitydiabetes mellitus type 2adenosine monophosphate-activated protein kinaseReferencesMiao 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.xMiao 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.xSoltis 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: 10.3109/10641969109042063Soltis 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: 10.3109/10641969109042063Lohn M. Periadventitial fat releases a vascular relaxing factor. The FASEB Journal. 2002;16(9):1057-63. doi: 10.1096/fj.02-0024comLohn M. Periadventitial fat releases a vascular relaxing factor. The FASEB Journal. 2002;16(9):1057-63. doi: 10.1096/fj.02-0024comAlmabrouk 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.12479Almabrouk 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.12479Barandier 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.01259.2004Barandier 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.01259.2004Souza 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.2006.04.002Souza 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.2006.04.002Wang 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/cvn288Wang 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/cvn288Takaoka 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.109.199653Takaoka 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.109.199653Frontini 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.2010.03.004Frontini 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.2010.03.004Chatterjee 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.108.182998Chatterjee 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.108.182998Ruan 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.110.215525Ruan 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.110.215525Meijer 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-yMeijer 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-yRajsheker 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-12-0232Rajsheker 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-12-0232Rodríguez 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.2006-0940Rodríguez 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.2006-0940Galvez 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.ddGalvez 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.ddThalmann S, Meier C. Local adipose tissue depots as cardiovascular risk factors. Cardiovascular Research. 2007;75(4):690-701. doi: 10.1016/j.cardiores.2007.03.008Thalmann S, Meier C. Local adipose tissue depots as cardiovascular risk factors. Cardiovascular Research. 2007;75(4):690-701. doi: 10.1016/j.cardiores.2007.03.008Cheng 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.0803726Cheng 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.0803726G. 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.1735G. 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.1735Greenstein 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.108.821181Greenstein 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.108.821181Lynch 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.00697.2012Lynch 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.00697.2012Zhu 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/cs20070347Zhu 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/cs20070347Ketonen 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-09-0661Ketonen 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-09-0661Marchesi 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.109.138305Marchesi 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.109.138305Meijer 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/db11-1603Meijer 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/db11-1603Lobato 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.2012.04.013Lobato 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.2012.04.013Szasz T, Bomfim Gf, Webb. The influence of perivascular adipose tissue on vascular homeostasis. Vascular Health and Risk Management. 2013:105. doi: 10.2147/vhrm.s33760Szasz T, Bomfim Gf, Webb. The influence of perivascular adipose tissue on vascular homeostasis. Vascular Health and Risk Management. 2013:105. doi: 10.2147/vhrm.s33760Yamawaki 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.2010.02.053Yamawaki 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.2010.02.053Gao 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.2006.03.013Gao 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.2006.03.013Wójcicka 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.2010.10.011Wójcicka 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.2010.10.011Lee 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.111.027375Lee 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.111.027375Lu 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.2011.01.023Lu 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.2011.01.023Rittig 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/s00125-012-2481-9Rittig 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/s00125-012-2481-9Mazurek T. Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators. Circulation. 2003;108(20):2460-6. doi: 10.1161/01.cir.0000099542.57313.c5Mazurek T. Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators. Circulation. 2003;108(20):2460-6. doi: 10.1161/01.cir.0000099542.57313.c5Rittig 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/s00125-008-1128-3Rittig 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/s00125-008-1128-3Goodpaster 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.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.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-zBarrett 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-zEringa 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: 10.1080/10739680701303584Eringa 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: 10.1080/10739680701303584Fernández-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: 10.1155/2013/402053Fernández-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: 10.1155/2013/402053Hayden 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: 10.1159/000329926Hayden 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: 10.1159/000329926Fitzgibbons 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.00376.2011Fitzgibbons 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.00376.2011Aghamohammadzadeh 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.2013.04.027Aghamohammadzadeh 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.2013.04.027Britton 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.112.004200Britton 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.112.004200Henrichot 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.0000188508.40052.35Henrichot 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.0000188508.40052.35Öhman 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.2011.07.012Öhman 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.2011.07.012Shyu 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/cs20100226Shyu 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/cs20100226Briones 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.111.190223Briones 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.111.190223Liao 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.34.2.201Liao 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.34.2.201Verhagen 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.2013.12.005Verhagen 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.2013.12.005Chang 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.112.104489Chang 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.112.104489Dong 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.2013.06.00Dong 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

The authors declare that there are no conflicts of interest present.