Роль периваскулярной жировой ткани в развитии сердечно-со- судистых заболеваний. Значение диагностики для оценки стра- тификации риска развития сердечно-сосудистых заболеваний
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Uchasova E.G., Gruzdeva O.V., Dyleva Y.A., Belik E.V. The role of perivascular adipose tissue in the development of cardiovascular diseases. The importance of diagnosis for assessing the risk stratification of cardiovascular diseases. Therapeutic Archive. 2019; 91 (4): 130–135. DOI: 10.26442/00403660.2019.04.000186
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Ключевые слова: ожирение, периваскулярная жировая ткань, эпикардиальная жировая ткань, адипоцитокины, адипонектин.
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Obesity is closely associated with metabolic and cardiovascular diseases, including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue (AT) is identified as a complex endocrine organ, with a wide range of regulatory functions at the cellular, tissue and systemic levels. Various terms, including paracardiac, epicardial and pericardial, are used to describe the fatty deposits surrounding the heart. Among all the fat depots, perivascular AT (PVAT) is of great biological significance for the cardiovascular system due to its anatomical proximity to the vessels. Recent studies have shown the presence of a complex, bidirectional paracrine and vasocardial signaling system between the vascular wall and PVAT. In the review, we will discuss the biological role of PVAT in both the physiological state and cardiovascular pathology, emphasizing its dual proatherogenic and antiatherogenic role. Let us consider PVAT as a target for various therapeutic agents in cardiovascular diseases. We will also analyze data on the role of non-invasive techniques as a diagnostic tool for assessing coronary artery inflammation.
Keywords: obesity, perivascular adipose tissue, epicardial adipose tissue, adipicytokines, adiponectin.
2. Antonopoulos AS, Oikonomou EK, Antoniades C, et al. From the BMI paradox to the obesity paradox: the obesity–mortality association in coronary heart disease. Obes Rev. 2016;17:989-1000. doi: 10.1111/obr.12440
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4. Fuster JJ, Ouchi N, Gokce N, et al. Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Circ Res. 2016;118:1786-807. doi: 10.1161/circresaha.115.306885
5. Отт А.В., Чумакова Г.А. Эпикардиальное ожирение как один из основных критериев метаболически тучного фенотипа ожирения и предикторов субклинического атеросклероза. Комплексные проблемы сердечно-сосудистых заболеваний. 2018;7(1):21-8 [Ott AV, Chumakova GA. Epicardial obesity as one of the main criteria of metabolic fat phenotype of obesity and predictors of subclinical atherosclerosis. Kompleksnye problemy serdechno-sosudistykh zabolevanii = Complex Issues of Cardiovascular Diseases. 2018;7(1):21-8 (In Russ.)]. doi: 10.17802/2306-1278-2018-7-1-21-28
6. Britton KA, Fox CS. Perivascular adipose tissue and vascular disease. Clin Lipidol. 2011;6:79-91. doi: 10.2217/clp.10.89
7. Груздева О.В., Акбашева О.Е., Дылева Ю.А. и др. Адипокиновый и цитокиновый профили эпикардиальной и подкожной жировой ткани у пациентов с ишемической болезнью сердца. Бюллетень экспериментальной биологии и медицины. 2017;163(5):560-3 [Gruzdeva OV, Akbasheva ОЕ, Dyleva YA. et.al. Adipokine and cytokine profile of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Byulleten' Eksperimental'noi Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2017;163(5):560-3 (In Russ.)].
8. Akoumianakis I, Antoniades C. The interplay between adipose tissue and the cardiovascular system: is fat always bad? Cardiovasc Res. 2017;113:999-1008. doi: 10.1093/cvr/cvx111
9. Patel VB, Shah S, Verma S, Oudit Gavin Y. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev. 2017;22(6):889-902. doi: 10.1007/s10741-017-9644-1
10. Antonopoulos AS, Sanna F, Sabharwal N, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017;9:eaal2658. doi: 10.1126/scitranslmed.aal2658
11. Margaritis M, Antonopoulos AS, Digby J, et al. 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. 2013;127:2209-21. doi: 10.1161/circulationaha.112.001133
12. Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens. 1991;A13:277-96. doi: 10.3109/10641969109042063
13. Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol. 2017;174:3425-42. doi: 10.1111/bph.13650
14. Akoumianakis I, Akawi N, Antoniades C. Exploring the crosstalk between adipose tissue and the cardiovascular system. Korean Circ J. 2017;47:670-85. doi: 10.4070/kcj.2017.0041
15. Goossens GH, Bizzarri A, Venteclef N, et al. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation. 2011;124:67-76. doi: 10.1161/circulationaha.111.027813
16. Gaborit B, Venteclef N, Ancel P, et al. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovasc Res. 2015;108:62-73. doi: 10.1093/cvr/cvv208
17. Salgado-Somoza A, Teijeira-Fernández E, Fernández AL, et al. Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress. Am J Physiol Heart Circ Physiol. 2010;299:202-9. doi: 10.1152/ajpheart.00120.2010
18. Vacca M, Di Eusanio M, Cariello M, et al. Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis. Cardiovasc Res. 2016;109:228-39. doi: 10.1093/cvr/cvv266
19. Sacks HS, Fain JN, Cheema P, et al. Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis. Metab Syndr Relat Disord. 2011;9:433-9. doi: 10.1089/met.2011.0024
20. Takaoka M, Suzuki H, Shioda S, et al. Endovascular injury induces rapid phenotypic changes in perivascular adipose tissue. Arterioscler Thromb Vasc Biol. 2010;30:1576-82. doi: 10.1161/atvbaha.110.207175
21. Akoumianakis I, Tarun A, Antoniades C. Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets. Br J Pharmacol. 2017;174:3411-24. doi: 10.1111/bph.13666
22. Iacobellis G, Lonn E, Lamy A, et al. Epicardial fat thickness and coronary artery disease correlate independently of obesity. Int J Cardiol. 2011;146:452-4. doi: 10.1016/j.ijcard.2010.10.117
23. Rosito GA, Massaro JM, Hoffmann U, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117:605-13. doi: 10.1161/circulationaha.107.743062
24. 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. 2009;30:850-6. doi: 10.1093/eurheartj/ehn573
25. McClain J, Hsu F, Brown E, et al. Pericardial adipose tissue and coronary artery calcification in the Multi-ethnic Study of Atherosclerosis (MESA). Obesity. 2013;21:1056-63. doi: 10.1002/oby.20090
26. Mahabadi AA, Lehmann N, Kälsch H, et al. Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study. JACC Cardiovasc Imaging. 2014;7:909-16. doi: 10.1016/j.jcmg.2014.07.002
27. Versteylen MO, Takx RA, Joosen IA, et al. Epicardial adipose tissue volume as a predictor for coronary artery disease in diabetic, impaired fasting glucose, and non-diabetic patients presenting with chest pain. Eur Heart J Cardiovasc Imaging. 2012;13:517-23. doi: 10.1093/ehjci/jes024
28. Hell MM, Ding X, Rubeaux M, et al. Epicardial adipose tissue volume but not density is an independent predictor for myocardial ischemia. J Cardiovasc Comput Tomogr. 2016;10:141-9. doi: 10.1016/j.jcct.2016.01.009
29. Груздева О.В., Бородкина Д.А., Акбашева О.Е. и др. Взаимосвязь толщины эпикардиальной и периваскулярной жировой ткани и адипокиново-цитокинового профиля пациентов с ишемической болезнью сердца в зависимости от наличия висцерального ожирения. Доктор.Ру. 2018;8(152):12-9 [Gruzdeva OV, Borodkina DA, Akbasheva ОЕ, et al. The Relationship Between Epicardial and Perivascular Adipose Tissue Thickness and Adipokine-Cytokine Profile in Ischemic Heart Disease Patients with and without Visceral Obesity. Doctor.Ru. 2018;8(152):12-9 (In Russ.)]. doi: 10.31550/1727-2378-2018-152-8-12-19
30. Iacobellis G, Kim MK, Franssens BT, Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol. 2018;71(20):2360-72. doi: 10.1016/j.jacc.2018.03.509
31. Franssens BT, Nathoe HM, Leiner T, et al. Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events. Eur J Prev Cardiol. 2017;24:660-70. doi: 10.1177/2047487316679524
32. Franssens BT, Nathoe HM, Visseren FL, et al. Relation of epicardial adipose tissue radiodensity to coronary artery calcium on cardiac computed tomography in patients at high risk for cardiovascular disease. Am J Cardiol. 2017;119:1359-65. doi: 10.1016/j.amjcard.2017.01.031
33. Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119-31.
34. Marwan M, Hell M, Schuhbäck A, et al. CT Attenuation of pericoronary adipose tissue in normal versus atherosclerotic coronary segments as defined by intravascular ultrasound. J Comput Assist Tomogr. 2017;41:762-7. doi: 10.1097/rct.0000000000000589
35. Ohyama K, Matsumoto Y, Takanami K, et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J Am Coll Cardiol. 2018;71:414-25. doi: 10.1016/j.jacc.2017.11.046
36. Alkhalil M, Edmond E, Edgar L, et al. The relationship of perivascular adipose tissue and atherosclerosis in the aorta and carotid arteries, determined by magnetic resonance imaging. Diab Vasc Dis Res. 2018;15:283-6. doi: 10.1177/1479164118757923
37. Shields KJ, El Khoudary SR, Ahearn JM, et al. Association of aortic perivascular adipose tissue density with aortic calcification in women with systemic lupus erythematosus. Atherosclerosis. 2017;262:55-61. doi: 10.1016/j.atherosclerosis.2017.04.021
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1. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-96. doi: 10.1016/s0140-6736(09)60318-4
2. Antonopoulos AS, Oikonomou EK, Antoniades C, et al. From the BMI paradox to the obesity paradox: the obesity–mortality association in coronary heart disease. Obes Rev. 2016;17:989-1000. doi: 10.1111/obr.12440
3. Gruzdeva OV, Akbasheva ОЕ, Borodkina DA, et al. The relationship of obesity and adipokines with the risk of type 2 diabetes a year after myocardial infarction. Rossiiskii Kardiologicheskii Zhurnal = Russ J Cardiol. 2015;(4):59-67 (in Russ.). doi: 10.15829/1560-4071-2015-4-59-67
4. Fuster JJ, Ouchi N, Gokce N, et al. Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Circ Res. 2016;118:1786-807. doi: 10.1161/circresaha.115.306885
5. Ott AV, Chumakova GA. Epicardial obesity as one of the main criteria of metabolic fat phenotype of obesity and predictors of subclinical atherosclerosis. Kompleksnye problemy serdechno-sosudistykh zabolevanii = Complex Issues of Cardiovascular Diseases. 2018;7(1):21-8 (In Russ.). doi: 10.17802/2306-1278-2018-7-1-21-28
6. Britton KA, Fox CS. Perivascular adipose tissue and vascular disease. Clin Lipidol. 2011;6:79-91. doi: 10.2217/clp.10.89
7. Gruzdeva OV, Akbasheva ОЕ, Dyleva YA. et.al. Adipokine and cytokine profile of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Byulleten' Eksperimental'noi Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2017;163(5):560-3 (In Russ.).
8. Akoumianakis I, Antoniades C. The interplay between adipose tissue and the cardiovascular system: is fat always bad? Cardiovasc Res. 2017;113:999-1008. doi: 10.1093/cvr/cvx111
9. Patel VB, Shah S, Verma S, Oudit Gavin Y. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev. 2017;22(6):889-902. doi: 10.1007/s10741-017-9644-1
10. Antonopoulos AS, Sanna F, Sabharwal N, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017;9:eaal2658. doi: 10.1126/scitranslmed.aal2658
11. Margaritis M, Antonopoulos AS, Digby J, et al. 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. 2013;127:2209-21. doi: 10.1161/circulationaha.112.001133
12. Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens. 1991;A13:277-96. doi: 10.3109/10641969109042063
13. Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol. 2017;174:3425-42. doi: 10.1111/bph.13650
14. Akoumianakis I, Akawi N, Antoniades C. Exploring the crosstalk between adipose tissue and the cardiovascular system. Korean Circ J. 2017;47:670-85. doi: 10.4070/kcj.2017.0041
15. Goossens GH, Bizzarri A, Venteclef N, et al. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation. 2011;124:67-76. doi: 10.1161/circulationaha.111.027813
16. Gaborit B, Venteclef N, Ancel P, et al. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. Cardiovasc Res. 2015;108:62-73. doi: 10.1093/cvr/cvv208
17. Salgado-Somoza A, Teijeira-Fernández E, Fernández AL, et al. Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress. Am J Physiol Heart Circ Physiol. 2010;299:202-9. doi: 10.1152/ajpheart.00120.2010
18. Vacca M, Di Eusanio M, Cariello M, et al. Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis. Cardiovasc Res. 2016;109:228-39. doi: 10.1093/cvr/cvv266
19. Sacks HS, Fain JN, Cheema P, et al. Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis. Metab Syndr Relat Disord. 2011;9:433-9. doi: 10.1089/met.2011.0024
20. Takaoka M, Suzuki H, Shioda S, et al. Endovascular injury induces rapid phenotypic changes in perivascular adipose tissue. Arterioscler Thromb Vasc Biol. 2010;30:1576-82. doi: 10.1161/atvbaha.110.207175
21. Akoumianakis I, Tarun A, Antoniades C. Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets. Br J Pharmacol. 2017;174:3411-24. doi: 10.1111/bph.13666
22. Iacobellis G, Lonn E, Lamy A, et al. Epicardial fat thickness and coronary artery disease correlate independently of obesity. Int J Cardiol. 2011;146:452-4. doi: 10.1016/j.ijcard.2010.10.117
23. Rosito GA, Massaro JM, Hoffmann U, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117:605-13. doi: 10.1161/circulationaha.107.743062
24. 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. 2009;30:850-6. doi: 10.1093/eurheartj/ehn573
25. McClain J, Hsu F, Brown E, et al. Pericardial adipose tissue and coronary artery calcification in the Multi-ethnic Study of Atherosclerosis (MESA). Obesity. 2013;21:1056-63. doi: 10.1002/oby.20090
26. Mahabadi AA, Lehmann N, Kälsch H, et al. Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study. JACC Cardiovasc Imaging. 2014;7:909-16. doi: 10.1016/j.jcmg.2014.07.002
27. Versteylen MO, Takx RA, Joosen IA, et al. Epicardial adipose tissue volume as a predictor for coronary artery disease in diabetic, impaired fasting glucose, and non-diabetic patients presenting with chest pain. Eur Heart J Cardiovasc Imaging. 2012;13:517-23. doi: 10.1093/ehjci/jes024
28. Hell MM, Ding X, Rubeaux M, et al. Epicardial adipose tissue volume but not density is an independent predictor for myocardial ischemia. J Cardiovasc Comput Tomogr. 2016;10:141-9. doi: 10.1016/j.jcct.2016.01.009
29. Gruzdeva OV, Borodkina DA, Akbasheva ОЕ, et al. The Relationship Between Epicardial and Perivascular Adipose Tissue Thickness and Adipokine-Cytokine Profile in Ischemic Heart Disease Patients with and without Visceral Obesity. Doctor.Ru. 2018;8(152):12-9 (In Russ.). doi: 10.31550/1727-2378-2018-152-8-12-19
30. Iacobellis G, Kim MK, Franssens BT, Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol. 2018;71(20):2360-72. doi: 10.1016/j.jacc.2018.03.509
31. Franssens BT, Nathoe HM, Leiner T, et al. Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events. Eur J Prev Cardiol. 2017;24:660-70. doi: 10.1177/2047487316679524
32. Franssens BT, Nathoe HM, Visseren FL, et al. Relation of epicardial adipose tissue radiodensity to coronary artery calcium on cardiac computed tomography in patients at high risk for cardiovascular disease. Am J Cardiol. 2017;119:1359-65. doi: 10.1016/j.amjcard.2017.01.031
33. Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119-31.
34. Marwan M, Hell M, Schuhbäck A, et al. CT Attenuation of pericoronary adipose tissue in normal versus atherosclerotic coronary segments as defined by intravascular ultrasound. J Comput Assist Tomogr. 2017;41:762-7. doi: 10.1097/rct.0000000000000589
35. Ohyama K, Matsumoto Y, Takanami K, et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J Am Coll Cardiol. 2018;71:414-25. doi: 10.1016/j.jacc.2017.11.046
36. Alkhalil M, Edmond E, Edgar L, et al. The relationship of perivascular adipose tissue and atherosclerosis in the aorta and carotid arteries, determined by magnetic resonance imaging. Diab Vasc Dis Res. 2018;15:283-6. doi: 10.1177/1479164118757923
37. Shields KJ, El Khoudary SR, Ahearn JM, et al. Association of aortic perivascular adipose tissue density with aortic calcification in women with systemic lupus erythematosus. Atherosclerosis. 2017;262:55-61. doi: 10.1016/j.atherosclerosis.2017.04.021
1 ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний», Кемерово, Россия;
2 ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России, Кемерово, Россия
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E.G. Uchasova 1, O.V. Gruzdeva 1,2, Yu.A. Dyleva 1, E.V. Belik 1
1 Research Institute for Complex Issues of Cardiovascular Disease, Kemerovo, Russia;
2 Kemerovo State Medical Academy of Ministry of Health of Russian Federation, Kemerovo, Russia