kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2024-13-1-179-195kpccz-1365Research ArticleОНЛАЙН. АНАЛИТИЧЕСКИЙ ОБЗОР. Патологическая физиология. Трансплантология и искусственные органыРОЛЬ АДИПОНЕКТИНА В АТЕРОГЕНЕЗЕ: ФУНДАМЕНТАЛЬНЫЕ АСПЕКТЫ И ПЕРСПЕКТИВЫ ТРАНСЛЯЦИИ В КЛИНИЧЕСКУЮ ПРАКТИКУROLE OF ADIPONECTIN IN ATHEROGENESIS: FUNDAMENTAL ASPECTS AND PERSPECTIVES IN TRANSLATION INTO CLINICAL PRACTICEhttps://orcid.org/0000-0002-5321-8834ТанянскийДмитрий АндреевичTanyanskiyDmitriy A.

доктор медицинских наук, доцент заведующий отделом биохимии федерального государственного бюджетного научного учреждения «Институт экспериментальной медицины», Санкт-Петербург, Российская Федерация; доцент кафедры фундаментальных проблем медицины и медицинских технологий федерального государственного бюджетного образовательного учреждения высшего образования «Санкт-Петербургский государственный университет», Санкт-Петербург, Российская Федерация; доцент кафедры биологической химии федерального государственного бюджетного образовательного учреждения высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской Федерации, Санкт-Петербург, Российская Федерация

PhD, Associate Professor, Head of the Department of Biochemistry, Federal State Budgetary Institution “Institute of Experimental Medicine”, Saint-Petersburg, Russian Federation; Associate Professor at the Department of Fundamental Issues of Medicine and Medical Technologies, Federal State Budgetary Educational Institution of Higher Education “Saint-Petersburg Petersburg State University”, Saint-Petersburg, Russian Federation; Associate Professor at the Department of Biological Chemistry, Federal State Budgetary Educational Institution of Higher Education “Academician I.P. Pavlov First Saint-Petersburg State Medical University” of the Ministry of Healthcare of Russian Federation, Saint-Petersburg, Russian Federation

dmitry.athero@gmail.comФедеральное государственное бюджетное научное учреждение «Институт Экспериментальной Медицины»; Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»; Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution “Institute of Experimental Medicine”; Federal State Budgetary Educational Institution of Higher Education “Saint-Petersburg State University”; Federal State Budgetary Educational Institution of Higher Education “Academician I.P. Pavlov First Saint-Petersburg State Medical University” of the Ministry of Healthcare of Russian FederationRussian Federation202429032024131179195Copyright © Танянский Д.А., 20242024Танянский Д.А.Tanyanskiy D.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/1365Основные положения

Основные положения

Приводится анализ литературных данных о физиологической роли адипонектина и механизмах его участия в атерогенезе. Рассмотрены перспективы трансляции имеющихся знаний в клиническую практику.

 

 

Резюме

Резюме

В обзоре рассматриваются вопросы физиологической роли адипонектина и его сигнальных механизмов. Проанализированы данные о путях и молекулярных механизмах участия адипонектина в атерогенезе, полученные на животных с экспериментальным атеросклерозом, образцах атеросклеротических бляшек и нормальных артерий человека, культивируемых эндотелиальных клетках, макрофагах и гладкомышечных клетках сосудов. Обсуждаются перспективы трансляции имеющихся знаний в клиническую практику.

Highlights

Highlights

The review presents the analysis of data on the physiological role and mechanisms of adiponectin in atherogenesis, and considers the prospects of transferring of existing knowledge into clinical practice.

 

 

Abstract

Abstract

The review is focused on the issues associated with the physiological role and signaling mechanisms of adiponectin. Data on the pathways and molecular mechanisms of adiponectin associated with atherogenesis was obtained using animal models with atherosclerosis, samples of atherosclerotic plaques and normal human arteries, cultured endothelial cells, macrophages and vascular smooth muscle. The perspectives of transferring of existing knowledge into clinical practice are discussed as well.

АдипонектинАтеросклерозЛипопротеины низкой плотностиЭндотелиальные клеткиМакрофагиAdiponectinAtherosclerosisLow-density lipoproteinsEndothelial cellsMacrophagesИсследования по влиянию адипонектина на функцию эндотелиальных клеток и макрофагов выполнены при поддержке гранта РНФ (проект № 22-25-00366).ReferencesLibby P., Bonow, R.O., Mann D.L., Tomaselli G.F., Bhatt D., Solomon S.D., Braunwald E. Braunwald's Heart Disease, 12th ed. Elsevier Inc.; 2022.Libby P., Bonow, R.O., Mann D.L., Tomaselli G.F., Bhatt D., Solomon S.D., Braunwald E. Braunwald's Heart Disease, 12th ed. Elsevier Inc.; 2022.Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288-298. doi: 10.1038/s41574-019-0176-8.Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288-298. doi: 10.1038/s41574-019-0176-8.Maya-Ramos L., Gillette T.G., Hill J.A., Scherer P.E. The Role of Adipose Tissue in Cardiovascular Pathophysiology. Cardiometab Syndr J. 2023;3(1):52-63. https://doi.org/10.51789/cmsj.2023.3.e9Maya-Ramos L., Gillette T.G., Hill J.A., Scherer P.E. The Role of Adipose Tissue in Cardiovascular Pathophysiology. Cardiometab Syndr J. 2023;3(1):52-63. https://doi.org/10.51789/cmsj.2023.3.e9Kern P.A., Di Gregorio G.B., Lu T., Rassouli N., Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003;52(7):1779-85. doi: 10.2337/diabetes.52.7.1779.Kern P.A., Di Gregorio G.B., Lu T., Rassouli N., Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003;52(7):1779-85. doi: 10.2337/diabetes.52.7.1779.Fu Y., Luo N., Klein R.L., Garvey W.T. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46(7):1369-79. doi: 10.1194/jlr.M400373-JLR200.Fu Y., Luo N., Klein R.L., Garvey W.T. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46(7):1369-79. doi: 10.1194/jlr.M400373-JLR200.Kim J.Y., van de Wall E., Laplante M., Azzara A., Trujillo M.E., Hofmann S.M., Schraw T., Durand J.L., Li H., Li G., Jelicks L.A., Mehler M.F., Hui D.Y., Deshaies Y., Shulman G.I., Schwartz G.J., Scherer P.E. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621-37. doi: 10.1172/JCI31021.Kim J.Y., van de Wall E., Laplante M., Azzara A., Trujillo M.E., Hofmann S.M., Schraw T., Durand J.L., Li H., Li G., Jelicks L.A., Mehler M.F., Hui D.Y., Deshaies Y., Shulman G.I., Schwartz G.J., Scherer P.E. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621-37. doi: 10.1172/JCI31021.Matsuura F., Oku H., Koseki M., Sandoval J.C., Yuasa-Kawase M., Tsubakio-Yamamoto K., Masuda D., Maeda N., Tsujii K., Ishigami M., Nishida M., Hirano K., Kihara S., Hori M., Shimomura I., Yamashita S. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun. 2007;358(4):1091-5. doi: 10.1016/j.bbrc.2007.05.040.Matsuura F., Oku H., Koseki M., Sandoval J.C., Yuasa-Kawase M., Tsubakio-Yamamoto K., Masuda D., Maeda N., Tsujii K., Ishigami M., Nishida M., Hirano K., Kihara S., Hori M., Shimomura I., Yamashita S. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun. 2007;358(4):1091-5. doi: 10.1016/j.bbrc.2007.05.040.Wang X., Chen Q., Pu H., Wei Q., Duan M., Zhang C., Jiang T., Shou X., Zhang J., Yang Y. Adiponectin improves NF-κB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice. Lipids Health Dis. 2016;15:33. doi: 10.1186/s12944-016-0202-y.Wang X., Chen Q., Pu H., Wei Q., Duan M., Zhang C., Jiang T., Shou X., Zhang J., Yang Y. Adiponectin improves NF-κB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice. Lipids Health Dis. 2016;15:33. doi: 10.1186/s12944-016-0202-y.Tsao T.S. Assembly of adiponectin oligomers. Rev Endocr Metab Disord. 2014;15(2):125-36. doi: 10.1007/s11154-013-9256-6.Tsao T.S. Assembly of adiponectin oligomers. Rev Endocr Metab Disord. 2014;15(2):125-36. doi: 10.1007/s11154-013-9256-6.Takemura Y., Ouchi N., Shibata R., Aprahamian T., Kirber M.T., Summer R.S., Kihara S., Walsh K. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117(2):375-86. doi: 10.1172/JCI29709.Takemura Y., Ouchi N., Shibata R., Aprahamian T., Kirber M.T., Summer R.S., Kihara S., Walsh K. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117(2):375-86. doi: 10.1172/JCI29709.Yamauchi T., Iwabu M., Okada-Iwabu M., Kadowaki T. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 2014;28(1):15-23. doi: 10.1016/j.beem.2013.09.003.Yamauchi T., Iwabu M., Okada-Iwabu M., Kadowaki T. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 2014;28(1):15-23. doi: 10.1016/j.beem.2013.09.003.Scherer P.E., Williams S., Fogliano M., Baldini G., Lodish H.F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270(45):26746-9. doi: 10.1074/jbc.270.45.26746.Scherer P.E., Williams S., Fogliano M., Baldini G., Lodish H.F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270(45):26746-9. doi: 10.1074/jbc.270.45.26746.Ding M., Carrão A.C., Wagner R.J., Xie Y., Jin Y., Rzucidlo E.M., Yu J., Li W., Tellides G., Hwa J., Aprahamian T.R., Martin K.A. Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol. 2012;52(2):474-84. doi: 10.1016/j.yjmcc.2011.09.008.Ding M., Carrão A.C., Wagner R.J., Xie Y., Jin Y., Rzucidlo E.M., Yu J., Li W., Tellides G., Hwa J., Aprahamian T.R., Martin K.A. Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol. 2012;52(2):474-84. doi: 10.1016/j.yjmcc.2011.09.008.Wong W.T., Tian X.Y., Xu A., Yu J., Lau C.W., Hoo R.L., Wang Y., Lee V.W., Lam K.S., Vanhoutte P.M., Huang Y. Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice. Cell Metab. 2011;14(1):104-15. doi: 10.1016/j.cmet.2011.05.009.Wong W.T., Tian X.Y., Xu A., Yu J., Lau C.W., Hoo R.L., Wang Y., Lee V.W., Lam K.S., Vanhoutte P.M., Huang Y. Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice. Cell Metab. 2011;14(1):104-15. doi: 10.1016/j.cmet.2011.05.009.Wedellová Z., Dietrich J., Siklová-Vítková M., Kološtová K., Kováčiková M., Dušková M., Brož J., Vedral T., Stich V., Polák J. Adiponectin inhibits spontaneous and catecholamine-induced lipolysis in human adipocytes of non-obese subjects through AMPK-dependent mechanisms. Physiol Res. 2011;60(1):139-48. doi: 10.33549/physiolres.931863.Wedellová Z., Dietrich J., Siklová-Vítková M., Kološtová K., Kováčiková M., Dušková M., Brož J., Vedral T., Stich V., Polák J. Adiponectin inhibits spontaneous and catecholamine-induced lipolysis in human adipocytes of non-obese subjects through AMPK-dependent mechanisms. Physiol Res. 2011;60(1):139-48. doi: 10.33549/physiolres.931863.Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y., Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M., Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P., Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-6. doi: 10.1038/90984.Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y., Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M., Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P., Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-6. doi: 10.1038/90984.Bruce C.R., Mertz V.A., Heigenhauser G.J.F., Dyck D.J. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes. 2005;54:3154-3160. doi: 10.2337/diabetes.54.11.3154.Bruce C.R., Mertz V.A., Heigenhauser G.J.F., Dyck D.J. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes. 2005;54:3154-3160. doi: 10.2337/diabetes.54.11.3154.Tanyanskiy D.A., Shavva V.S., Dizhe E.B., Oleinikova G.N., Lizunov A.V., Nekrasova E.V., Mogilenko D.A., Larionova E.E., Orlov S.V., Denisenko A.D. Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms. Biochemistry (Mosc). 2022;87(11):1252-1259. doi: 10.1134/S0006297922110049.Tanyanskiy D.A., Shavva V.S., Dizhe E.B., Oleinikova G.N., Lizunov A.V., Nekrasova E.V., Mogilenko D.A., Larionova E.E., Orlov S.V., Denisenko A.D. Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms. Biochemistry (Mosc). 2022;87(11):1252-1259. doi: 10.1134/S0006297922110049.Tschritter O., Fritsche A., Thamer C., Haap M., Shirkavand F., Rahe S., Staiger H., Maerker E., Häring H., Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes. 2003;52(2):239-43. doi: 10.2337/diabetes.52.2.239.Tschritter O., Fritsche A., Thamer C., Haap M., Shirkavand F., Rahe S., Staiger H., Maerker E., Häring H., Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes. 2003;52(2):239-43. doi: 10.2337/diabetes.52.2.239.Zhou L., Deepa S.S., Etzler J.C., Ryu J., Mao X., Fang Q., Liu D.D., Torres J.M., Jia W., Lechleiter J.D., Liu F., Dong L.Q. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways. J Biol Chem. 2009;284(33):22426-22435. doi: 10.1074/jbc.M109.028357.Zhou L., Deepa S.S., Etzler J.C., Ryu J., Mao X., Fang Q., Liu D.D., Torres J.M., Jia W., Lechleiter J.D., Liu F., Dong L.Q. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways. J Biol Chem. 2009;284(33):22426-22435. doi: 10.1074/jbc.M109.028357.Mao X., Kikani C.K., Riojas R.A., Langlais P., Wang L., Ramos F.J., Fang Q., Christ-Roberts C.Y., Hong J.Y., Kim R.Y., Liu F., Dong L.Q. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol. 2006;8(5):516-23. doi: 10.1038/ncb1404.Mao X., Kikani C.K., Riojas R.A., Langlais P., Wang L., Ramos F.J., Fang Q., Christ-Roberts C.Y., Hong J.Y., Kim R.Y., Liu F., Dong L.Q. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol. 2006;8(5):516-23. doi: 10.1038/ncb1404.Yoon Y.S., Ryu D., Lee M.W., Hong S., Koo S.H. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis. Exp Mol Med. 2009;41(8):577-583. https://doi.org/10.3858/emm.2009.41.8.063Yoon Y.S., Ryu D., Lee M.W., Hong S., Koo S.H. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis. Exp Mol Med. 2009;41(8):577-583. https://doi.org/10.3858/emm.2009.41.8.063Hug C., Wang J., Ahmad N.S., Bogan J.S., Tsao T.S., Lodish H.F. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci U S A. 2004;101(28):10308-13. doi: 10.1073/pnas.0403382101.Hug C., Wang J., Ahmad N.S., Bogan J.S., Tsao T.S., Lodish H.F. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci U S A. 2004;101(28):10308-13. doi: 10.1073/pnas.0403382101.Matsuda K., Fujishima Y., Maeda N., Mori T., Hirata A., Sekimoto R., Tsushima Y., Masuda S., Yamaoka M., Inoue K., Nishizawa H., Kita S., Ranscht B., Funahashi T., Shimomura I. Positive feedback regulation between adiponectin and T-cadherin impacts adiponectin levels in tissue and plasma of male mice. Endocrinology. 2015;156(3):934-46. doi: 10.1210/en.2014-1618.Matsuda K., Fujishima Y., Maeda N., Mori T., Hirata A., Sekimoto R., Tsushima Y., Masuda S., Yamaoka M., Inoue K., Nishizawa H., Kita S., Ranscht B., Funahashi T., Shimomura I. Positive feedback regulation between adiponectin and T-cadherin impacts adiponectin levels in tissue and plasma of male mice. Endocrinology. 2015;156(3):934-46. doi: 10.1210/en.2014-1618.Wang Y., Zheng A., Yan Y., Song F., Kong Q., Qin S., Zhang D. Association between HMW adiponectin, HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population. Atherosclerosis. 2014;235(2):392-7. doi: 10.1016/j.atherosclerosis.2014.05.910.Wang Y., Zheng A., Yan Y., Song F., Kong Q., Qin S., Zhang D. Association between HMW adiponectin, HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population. Atherosclerosis. 2014;235(2):392-7. doi: 10.1016/j.atherosclerosis.2014.05.910.Wu Z.J., Cheng Y.J., Gu W.J., Aung L.H. Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism. 2014;63(9):1157-66. doi: 10.1016/j.metabol.2014.05.001.Wu Z.J., Cheng Y.J., Gu W.J., Aung L.H. Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism. 2014;63(9):1157-66. doi: 10.1016/j.metabol.2014.05.001.Okamoto Y., Kihara S., Ouchi N., Nishida M., Arita Y., Kumada M., Ohashi K., Sakai N., Shimomura I., Kobayashi H., Terasaka N., Inaba T., Funahashi T., Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106(22):2767-70. doi: 10.1161/01.cir.0000042707.50032.19.Okamoto Y., Kihara S., Ouchi N., Nishida M., Arita Y., Kumada M., Ohashi K., Sakai N., Shimomura I., Kobayashi H., Terasaka N., Inaba T., Funahashi T., Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106(22):2767-70. doi: 10.1161/01.cir.0000042707.50032.19.Yamauchi T., Kamon J., Waki H., Imai Y., Shimozawa N., Hioki K., Uchida S., Ito Y., Takakuwa K., Matsui J., Takata M., Eto K., Terauchi Y., Komeda K., Tsunoda M., Murakami K., Ohnishi Y., Naitoh T., Yamamura K., Ueyama Y., Froguel P., Kimura S., Nagai R., Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278(4):2461-8. doi: 10.1074/jbc.M209033200.Yamauchi T., Kamon J., Waki H., Imai Y., Shimozawa N., Hioki K., Uchida S., Ito Y., Takakuwa K., Matsui J., Takata M., Eto K., Terauchi Y., Komeda K., Tsunoda M., Murakami K., Ohnishi Y., Naitoh T., Yamamura K., Ueyama Y., Froguel P., Kimura S., Nagai R., Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278(4):2461-8. doi: 10.1074/jbc.M209033200.van Stijn C.M., Kim J., Barish G.D., Tietge U.J., Tangirala R.K. Adiponectin expression protects against angiotensin II-mediated inflammation and accelerated atherosclerosis. PLoS One. 2014;9(1):e86404. doi: 10.1371/journal.pone.0086404.van Stijn C.M., Kim J., Barish G.D., Tietge U.J., Tangirala R.K. Adiponectin expression protects against angiotensin II-mediated inflammation and accelerated atherosclerosis. PLoS One. 2014;9(1):e86404. doi: 10.1371/journal.pone.0086404.Li L., Cai X.J., Feng M., Rong Y.Y., Zhang Y., Zhang M. Effect of adiponectin overexpression on stability of preexisting plaques by inducing prolyl-4-hydroxylase expression. Circ J. 2010;74(3):552-9. doi: 10.1253/circj.cj-09-0304.Li L., Cai X.J., Feng M., Rong Y.Y., Zhang Y., Zhang M. Effect of adiponectin overexpression on stability of preexisting plaques by inducing prolyl-4-hydroxylase expression. Circ J. 2010;74(3):552-9. doi: 10.1253/circj.cj-09-0304.Okamoto Y., Folco E.J., Minami M., Wara A.K., Feinberg M.W., Sukhova G.K., Colvin R.A., Kihara S., Funahashi T., Luster A.D., Libby P. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102(2):218-25. doi: 10.1161/CIRCRESAHA.107.164988.Okamoto Y., Folco E.J., Minami M., Wara A.K., Feinberg M.W., Sukhova G.K., Colvin R.A., Kihara S., Funahashi T., Luster A.D., Libby P. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102(2):218-25. doi: 10.1161/CIRCRESAHA.107.164988.Nawrocki A.R., Hofmann S.M., Teupser D., Basford J.E., Durand J.L., Jelicks L.A., Woo C.W., Kuriakose G., Factor S.M., Tanowitz H.B., Hui D.Y., Tabas I., Scherer P.E. Lack of association between adiponectin levels and atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2010;30(6):1159-65. doi: 10.1161/ATVBAHA.109.195826.Nawrocki A.R., Hofmann S.M., Teupser D., Basford J.E., Durand J.L., Jelicks L.A., Woo C.W., Kuriakose G., Factor S.M., Tanowitz H.B., Hui D.Y., Tabas I., Scherer P.E. Lack of association between adiponectin levels and atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2010;30(6):1159-65. doi: 10.1161/ATVBAHA.109.195826.Li C.J., Sun H.W., Zhu F.L., Chen L., Rong Y.Y., Zhang Y., Zhang M. Local adiponectin treatment reduces atherosclerotic plaque size in rabbits. J Endocrinol. 2007;193(1):137-45. doi: 10.1677/JOE-06-0173.Li C.J., Sun H.W., Zhu F.L., Chen L., Rong Y.Y., Zhang Y., Zhang M. Local adiponectin treatment reduces atherosclerotic plaque size in rabbits. J Endocrinol. 2007;193(1):137-45. doi: 10.1677/JOE-06-0173.Cai X., Li X., Li L., Huang X.Z., Liu Y.S., Chen L., Zhang K., Wang L., Li X., Song J., Li S., Zhang Y., Zhang M. Adiponectin reduces carotid atherosclerotic plaque formation in ApoE-/- mice: roles of oxidative and nitrosative stress and inducible nitric oxide synthase. Mol Med Rep. 2015;11(3):1715-21. doi: 10.3892/mmr.2014.2947.Cai X., Li X., Li L., Huang X.Z., Liu Y.S., Chen L., Zhang K., Wang L., Li X., Song J., Li S., Zhang Y., Zhang M. Adiponectin reduces carotid atherosclerotic plaque formation in ApoE-/- mice: roles of oxidative and nitrosative stress and inducible nitric oxide synthase. Mol Med Rep. 2015;11(3):1715-21. doi: 10.3892/mmr.2014.2947.Gasbarrino K., Zheng H., Hafiane A., Veinot J.P., Lai C., Daskalopoulou S.S. Decreased Adiponectin-Mediated Signaling Through the AdipoR2 Pathway Is Associated With Carotid Plaque Instability. Stroke. 2017;48(4):915-924. doi: 10.1161/STROKEAHA.116.015145.Gasbarrino K., Zheng H., Hafiane A., Veinot J.P., Lai C., Daskalopoulou S.S. Decreased Adiponectin-Mediated Signaling Through the AdipoR2 Pathway Is Associated With Carotid Plaque Instability. Stroke. 2017;48(4):915-924. doi: 10.1161/STROKEAHA.116.015145.Tanyanskiy D.A., Pigarevskii P.V., Maltseva S.V., Denisenko A.D. Immunohistochemical analysis of adiponectin in atherosclerotic lesions of human aorta. ARYA Atheroscler. 2019; 15(4): 179-84. doi: 10.22122/arya.v15i4.1873.Tanyanskiy D.A., Pigarevskii P.V., Maltseva S.V., Denisenko A.D. Immunohistochemical analysis of adiponectin in atherosclerotic lesions of human aorta. ARYA Atheroscler 2019; 15(4): 179-84.Танянский Д.А., Пигаревский П.В., Мальцева С.В., Малашичева А.Б., Докшин П.М., Успенский В.Е., Лизунов А.В., Орлов С.В., Мальцева О.Н., Агеева Е.В., Денисенко А.Д. Адипонектин в нормальной и атеросклеротически измененной интиме аорты человека. Архив патологии. 2022;84(6):16 22. doi: 10.17116/patol20228406116.Tanyanskiy D.A., Pigarevsky P.V., Maltseva S.V., Malashicheva A.B., Docshin P.M., Uspensky V.E., Lizunov A.V., Orlov S.V., Maltseva O.N., Ageeva E.V., Denisenko A.D. Adiponectin in normal and atherosclerotic intima of human aorta. Arkhiv Patologii. 2022;84(6):16-22. (In Russ.). https://doi.org/10.17116/patol20228406116Kostopoulos C.G., Spiroglou S.G., Varakis J.N., Apostolakis E., Papadaki H.H. Adiponectin/T-cadherin and apelin/APJ expression in human arteries and periadventitial fat: implication of local adipokine signaling in atherosclerosis? Cardiovasc Pathol. 2014;23(3):131-8. doi: 10.1016/j.carpath.2014.02.003.Kostopoulos C.G., Spiroglou S.G., Varakis J.N., Apostolakis E., Papadaki H.H. Adiponectin/T-cadherin and apelin/APJ expression in human arteries and periadventitial fat: implication of local adipokine signaling in atherosclerosis? Cardiovasc Pathol. 2014;23(3):131-8. doi: 10.1016/j.carpath.2014.02.003.Xu S.Q., Mahadev K., Wu X., Fuchsel L., Donnelly S., Scalia R.G., Goldstein B.J. Adiponectin protects against angiotensin II or tumor necrosis factor alpha-induced endothelial cell monolayer hyperpermeability: role of cAMP/PKA signaling. Arterioscler Thromb Vasc Biol. 2008;28(5):899-905. doi: 10.1161/ATVBAHA.108.163634.Xu S.Q., Mahadev K., Wu X., Fuchsel L., Donnelly S., Scalia R.G., Goldstein B.J. Adiponectin protects against angiotensin II or tumor necrosis factor alpha-induced endothelial cell monolayer hyperpermeability: role of cAMP/PKA signaling. Arterioscler Thromb Vasc Biol. 2008;28(5):899-905. doi: 10.1161/ATVBAHA.108.163634.Танянский Д.А., Мальцева О.Н., Трулев А.С., Сагинбаев У.Р., Евстигнеева П.Е., Воронкина И.В., Смагина Л.В., Иванова А.А., Дмитриева А.А., Агеева Е.В., Салль Т.С., Денисенко А.Д. Влияние адипонектина на транспорт липопротеинов низкой плотности через монослой эндотелиальных клеток человека in vitro. Бюллетень экспериментальной биологии и медицины. 2023;176(8): 192-197. doi: 10.47056/0365-9615-2023-176-8-192-197.Tanyanskiy D.A., Maltseva O.N., Trulioff A.S., Saginbaev U.R., Evstigneeva P.E., Voronkina I.V., Smagina L.V., Ivanova A.A., Dmitrieva A.A., Ageeva E.V., Sall T.S., Denisenko A.D. The influence of adiponectin on transport of low-density lipoproteins through human endothelial cells monolayer in vitro. Bull Exp Biol Med. 2023;176(8): 192-197. (In Russ.). doi: 10.47056/0365-9615-2023-176-8-192-197.Hattori Y., Hattori S., Kasai K. Globular adiponectin activates nuclear factor-kappaB in vascular endothelial cells, which in turn induces expression of proinflammatory and adhesion molecule genes. Diabetes Care. 2006;29(1):139-41. doi: 10.2337/diacare.29.1.139.Hattori Y., Hattori S., Kasai K. Globular adiponectin activates nuclear factor-kappaB in vascular endothelial cells, which in turn induces expression of proinflammatory and adhesion molecule genes. Diabetes Care. 2006;29(1):139-41. doi: 10.2337/diacare.29.1.139.Addabbo F. Nacci C., De Benedictis L., Leo V., Tarquinio M., Quon M.J., Montagnani M. Globular adiponectin counteracts VCAM-1-mediated monocyte adhesion via AdipoR1/NF-κB/COX-2 signaling in human aortic endothelial cells. Am J Physiol Endocrinol Metab. 2011;301(6):E1143-54. doi: 10.1152/ajpendo.00208.2011.Addabbo F. Nacci C., De Benedictis L., Leo V., Tarquinio M., Quon M.J., Montagnani M. Globular adiponectin counteracts VCAM-1-mediated monocyte adhesion via AdipoR1/NF-κB/COX-2 signaling in human aortic endothelial cells. Am J Physiol Endocrinol Metab. 2011;301(6):E1143-54. doi: 10.1152/ajpendo.00208.2011.Lee Y.A., Ji H.I., Lee S.H., Hong S.J., Yang H.I., Chul Yoo M., Kim K.S. The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints. Exp Mol Med. 2014;46(1):e72. doi: 10.1038/emm.2013.141.Lee Y.A., Ji H.I., Lee S.H., Hong S.J., Yang H.I., Chul Yoo M., Kim K.S. The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints. Exp Mol Med. 2014;46(1):e72. doi: 10.1038/emm.2013.141.Wang Y., Wang X., Lau W.B., Yuan Y., Booth D., Li J.J., Scalia R., Preston K., Gao E., Koch W., Ma X.L. Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res. 2014;114(5):792-805. doi: 10.1161/CIRCRESAHA.114.302439.Wang Y., Wang X., Lau W.B., Yuan Y., Booth D., Li J.J., Scalia R., Preston K., Gao E., Koch W., Ma X.L. Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res. 2014;114(5):792-805. doi: 10.1161/CIRCRESAHA.114.302439.Bråkenhielm E., Veitonmäki N., Cao R., Kihara S., Matsuzawa Y., Zhivotovsky B., Funahashi T., Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101(8):2476-81. doi: 10.1073/pnas.0308671100.Bråkenhielm E., Veitonmäki N., Cao R., Kihara S., Matsuzawa Y., Zhivotovsky B., Funahashi T., Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101(8):2476-81. doi: 10.1073/pnas.0308671100.Mahadev K., Wu X., Donnelly S., Ouedraogo R., Eckhart A.D., Goldstein B.J. Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells. Cardiovasc Res. 2008;78(2):376-84. doi: 10.1093/cvr/cvn034.Mahadev K., Wu X., Donnelly S., Ouedraogo R., Eckhart A.D., Goldstein B.J. Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells. Cardiovasc Res. 2008;78(2):376-84. doi: 10.1093/cvr/cvn034.Ouchi N., Kobayashi H., Kihara S., Kumada M., Sato K., Inoue T., Funahashi T., Walsh K. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279(2):1304-9. doi: 10.1074/jbc.M310389200.Ouchi N., Kobayashi H., Kihara S., Kumada M., Sato K., Inoue T., Funahashi T., Walsh K. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279(2):1304-9. doi: 10.1074/jbc.M310389200.Shibata R., Ouchi N., Kihara S., Sato K., Funahashi T., Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004;279(27):28670-4. doi: 10.1074/jbc.M402558200.Shibata R., Ouchi N., Kihara S., Sato K., Funahashi T., Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004;279(27):28670-4. doi: 10.1074/jbc.M402558200.Alvarez G., Visitación Bartolomé M., Miana M., Jurado-López R., Martín R., Zuluaga P., Martinez-Martinez E., Nieto M.L., Alvarez-Sala L.A., Millán J., Lahera V., Cachofeiro V. The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study. J Vasc Res. 2012;49(2):111-22. doi: 10.1159/000332332.Alvarez G., Visitación Bartolomé M., Miana M., Jurado-López R., Martín R., Zuluaga P., Martinez-Martinez E., Nieto M.L., Alvarez-Sala L.A., Millán J., Lahera V., Cachofeiro V. The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study. J Vasc Res. 2012;49(2):111-22. doi: 10.1159/000332332.Adya R., Tan B.K., Chen J., Randeva H.S. Protective actions of globular and full-length adiponectin on human endothelial cells: novel insights into adiponectin-induced angiogenesis. J Vasc Res. 2012;49(6):534-43. doi: 10.1159/000338279.Adya R., Tan B.K., Chen J., Randeva H.S. Protective actions of globular and full-length adiponectin on human endothelial cells: novel insights into adiponectin-induced angiogenesis. J Vasc Res. 2012;49(6):534-43. doi: 10.1159/000338279.Tian L., Luo N., Zhu X., Chung B.H., Garvey W.T., Fu Y. Adiponectin-AdipoR1/2-APPL1 signaling axis suppresses human foam cell formation: differential ability of AdipoR1 and AdipoR2 to regulate inflammatory cytokine responses. Atherosclerosis. 2012;221(1):66-75. doi: 10.1016/j.atherosclerosis.2011.12.014.Tian L., Luo N., Zhu X., Chung B.H., Garvey W.T., Fu Y. Adiponectin-AdipoR1/2-APPL1 signaling axis suppresses human foam cell formation: differential ability of AdipoR1 and AdipoR2 to regulate inflammatory cytokine responses. Atherosclerosis. 2012;221(1):66-75. doi: 10.1016/j.atherosclerosis.2011.12.014.Tsubakio-Yamamoto K., Matsuura F., Koseki M., Oku H., Sandoval J.C., Inagaki M., Nakatani K., Nakaoka H., Kawase R., Yuasa-Kawase M., Masuda D., Ohama T., Maeda N., Nakagawa-Toyama Y., Ishigami M., Nishida M., Kihara S., Shimomura I., Yamashita S. Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem Biophys Res Commun. 2008;375(3):390-4. doi: 10.1016/j.bbrc.2008.08.009.Tsubakio-Yamamoto K., Matsuura F., Koseki M., Oku H., Sandoval J.C., Inagaki M., Nakatani K., Nakaoka H., Kawase R., Yuasa-Kawase M., Masuda D., Ohama T., Maeda N., Nakagawa-Toyama Y., Ishigami M., Nishida M., Kihara S., Shimomura I., Yamashita S. Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem Biophys Res Commun. 2008;375(3):390-4. doi: 10.1016/j.bbrc.2008.08.009.Haugen F., Drevon C.A. Activation of nuclear factor-kappaB by high molecular weight and globular adiponectin. Endocrinology. 2007;148(11):5478-86. doi: 10.1210/en.2007-0370.Haugen F., Drevon C.A. Activation of nuclear factor-kappaB by high molecular weight and globular adiponectin. Endocrinology. 2007;148(11):5478-86. doi: 10.1210/en.2007-0370.Kyriazi E., Tsiotra P.C., Boutati E., Ikonomidis I., Fountoulaki K., Maratou E., Lekakis J., Dimitriadis G., Kremastinos D.T., Raptis S.A. Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages. Horm Metab Res. 2011;43(8):537-44. doi: 10.1055/s-0031-1277227.Kyriazi E., Tsiotra P.C., Boutati E., Ikonomidis I., Fountoulaki K., Maratou E., Lekakis J., Dimitriadis G., Kremastinos D.T., Raptis S.A. Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages. Horm Metab Res. 2011;43(8):537-44. doi: 10.1055/s-0031-1277227.Folco E.J., Rocha V.Z., López-Ilasaca M., Libby P. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem. 2009;284(38):25569-75. doi: 10.1074/jbc.M109.019786.Folco E.J., Rocha V.Z., López-Ilasaca M., Libby P. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem. 2009;284(38):25569-75. doi: 10.1074/jbc.M109.019786.Lovren F., Pan Y., Quan A., Szmitko P.E., Singh K.K., Shukla P.C., Gupta M., Chan L., Al-Omran M., Teoh H., Verma S. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol. 2010;299(3):H656-63. doi: 10.1152/ajpheart.00115.2010.Lovren F., Pan Y., Quan A., Szmitko P.E., Singh K.K., Shukla P.C., Gupta M., Chan L., Al-Omran M., Teoh H., Verma S. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol. 2010;299(3):H656-63. doi: 10.1152/ajpheart.00115.2010.Mandal P., Pratt B.T., Barnes M., McMullen M.R., Nagy L.E. Molecular mechanism for adiponectin-dependent M2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin. J Biol Chem. 2011;286(15):13460-9. doi: 10.1074/jbc.M110.204644.Mandal P., Pratt B.T., Barnes M., McMullen M.R., Nagy L.E. Molecular mechanism for adiponectin-dependent M2 macrophage polarization: link between the metabolic and innate immune activity of full-length adiponectin. J Biol Chem. 2011;286(15):13460-9. doi: 10.1074/jbc.M110.204644.Bi Y., Chen J., Hu F., Liu J., Li M., Zhao L. M2 Macrophages as a Potential Target for Antiatherosclerosis Treatment. Neural Plast. 2019;2019:6724903. doi: 10.1155/2019/6724903.Bi Y., Chen J., Hu F., Liu J., Li M., Zhao L. M2 Macrophages as a Potential Target for Antiatherosclerosis Treatment. Neural Plast. 2019;2019:6724903. doi: 10.1155/2019/6724903.Kumada M., Kihara S., Ouchi N., Kobayashi H., Okamoto Y., Ohashi K., Maeda K., Nagaretani H., Kishida K., Maeda N., Nagasawa A., Funahashi T., Matsuzawa Y. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004;109(17):2046-9. doi: 10.1161/01.CIR.0000127953.98131.ED.Kumada M., Kihara S., Ouchi N., Kobayashi H., Okamoto Y., Ohashi K., Maeda K., Nagaretani H., Kishida K., Maeda N., Nagasawa A., Funahashi T., Matsuzawa Y. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004;109(17):2046-9. doi: 10.1161/01.CIR.0000127953.98131.ED.Summer R., Little F.F., Ouchi N., Takemura Y., Aprahamian T., Dwyer D., Fitzsimmons K., Suki B., Parameswaran H., Fine A., Walsh K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):L1035-42. doi: 10.1152/ajplung.00397.2007.Summer R., Little F.F., Ouchi N., Takemura Y., Aprahamian T., Dwyer D., Fitzsimmons K., Suki B., Parameswaran H., Fine A., Walsh K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):L1035-42. doi: 10.1152/ajplung.00397.2007.Matsuda M., Shimomura I., Sata M., Arita Y., Nishida M., Maeda N., Kumada M., Okamoto Y., Nagaretani H., Nishizawa H., Kishida K., Komuro R., Ouchi N., Kihara S., Nagai R., Funahashi T., Matsuzawa Y. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002;277(40):37487-91. doi: 10.1074/jbc.M206083200.Matsuda M., Shimomura I., Sata M., Arita Y., Nishida M., Maeda N., Kumada M., Okamoto Y., Nagaretani H., Nishizawa H., Kishida K., Komuro R., Ouchi N., Kihara S., Nagai R., Funahashi T., Matsuzawa Y. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002;277(40):37487-91. doi: 10.1074/jbc.M206083200.Motobayashi Y., Izawa-Ishizawa Y., Ishizawa K., Orino S., Yamaguchi K., Kawazoe K., Hamano S., Tsuchiya K., Tomita S., Tamaki T. Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells. Hypertens Res. 2009;32(3):188-93. doi: 10.1038/hr.2008.19.Motobayashi Y., Izawa-Ishizawa Y., Ishizawa K., Orino S., Yamaguchi K., Kawazoe K., Hamano S., Tsuchiya K., Tomita S., Tamaki T. Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells. Hypertens Res. 2009;32(3):188-93. doi: 10.1038/hr.2008.19.Zhang W., Shu C., Li Q., Li M., Li X. Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway. Mol Med Rep. 2015;12(3):4703-4707. doi: 10.3892/mmr.2015.3899.Zhang W., Shu C., Li Q., Li M., Li X. Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway. Mol Med Rep. 2015;12(3):4703-4707. doi: 10.3892/mmr.2015.3899.Ding M., Xie Y., Wagner R.J., Jin Y., Carrao A.C., Liu L.S., Guzman A.K., Powell R.J., Hwa J., Rzucidlo E.M., Martin K.A. Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4. Arterioscler Thromb Vasc Biol. 2011;31(6):1403-10. doi: 10.1161/ATVBAHA.110.216804.Ding M., Xie Y., Wagner R.J., Jin Y., Carrao A.C., Liu L.S., Guzman A.K., Powell R.J., Hwa J., Rzucidlo E.M., Martin K.A. Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4. Arterioscler Thromb Vasc Biol. 2011;31(6):1403-10. doi: 10.1161/ATVBAHA.110.216804.Tanabe H., Fujii Y., Okada-Iwabu M., Iwabu M., Nakamura Y., Hosaka T., Motoyama K., Ikeda M., Wakiyama M., Terada T., Ohsawa N., Hato M., Ogasawara S., Hino T., Murata T., Iwata S., Hirata K., Kawano Y., Yamamoto M., Kimura-Someya T., Shirouzu M., Yamauchi T., Kadowaki T., Yokoyama S. Crystal structures of the human adiponectin receptors. Nature. 2015;520(7547):312-316. doi: 10.1038/nature14301Tanabe H., Fujii Y., Okada-Iwabu M., Iwabu M., Nakamura Y., Hosaka T., Motoyama K., Ikeda M., Wakiyama M., Terada T., Ohsawa N., Hato M., Ogasawara S., Hino T., Murata T., Iwata S., Hirata K., Kawano Y., Yamamoto M., Kimura-Someya T., Shirouzu M., Yamauchi T., Kadowaki T., Yokoyama S. Crystal structures of the human adiponectin receptors. Nature. 2015;520(7547):312-316. doi: 10.1038/nature14301Otvos L. Jr, Haspinger E., La Russa F., Maspero F., Graziano P., Kovalszky I., Lovas S., Nama K., Hoffmann R., Knappe D., Cassone M., Wade J., Surmacz E. Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. BMC Biotechnol. 2011;11:90. doi: 10.1186/1472-6750-11-90.Otvos L. Jr, Haspinger E., La Russa F., Maspero F., Graziano P., Kovalszky I., Lovas S., Nama K., Hoffmann R., Knappe D., Cassone M., Wade J., Surmacz E. Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. BMC Biotechnol. 2011;11:90. doi: 10.1186/1472-6750-11-90.Sung H.K., Mitchell P.L., Gross S., Marette A., Sweeney G. ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells. Am J Physiol Cell Physiol. 2022;322(2):C151-C163. doi: 10.1152/ajpcell.00603.2020.Sung H.K., Mitchell P.L., Gross S., Marette A., Sweeney G. ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells. Am J Physiol Cell Physiol. 2022;322(2):C151-C163. doi: 10.1152/ajpcell.00603.2020.Sun L., Yang X., Li Q., Zeng P., Liu Y., Liu L., Chen Y., Yu M., Ma C., Li X., Li Y., Zhang R., Zhu Y., Miao Q.R., Han J., Duan Y. Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice. Arterioscler Thromb Vasc Biol. 2017;37(7):1290-1300. doi: 10.1161/ATVBAHA.117.309630.Sun L., Yang X., Li Q., Zeng P., Liu Y., Liu L., Chen Y., Yu M., Ma C., Li X., Li Y., Zhang R., Zhu Y., Miao Q.R., Han J., Duan Y. Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice. Arterioscler Thromb Vasc Biol. 2017;37(7):1290-1300. doi: 10.1161/ATVBAHA.117.309630.Xu H., Zhao Q., Song N., Yan Z., Lin R., Wu S., Jiang L., Hong S., Xie J., Zhou H., Wang R., Jiang X. AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nat Commun. 2020;11(1):5807. doi: 10.1038/s41467-020-19668-y.Xu H., Zhao Q., Song N., Yan Z., Lin R., Wu S., Jiang L., Hong S., Xie J., Zhou H., Wang R., Jiang X. AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nat Commun. 2020;11(1):5807. doi: 10.1038/s41467-020-19668-y.Lee I.K., Kim G., Kim D.H., Kim B.B. PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2. Int J Mol Sci. 2021;22(2):884. doi: 10.3390/ijms22020884.Lee I.K., Kim G., Kim D.H., Kim B.B. PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2. Int J Mol Sci. 2021;22(2):884. doi: 10.3390/ijms22020884.Okada-Iwabu M., Yamauchi T., Iwabu M., Honma T., Hamagami K., Matsuda K., Yamaguchi M., Tanabe H., Kimura-Someya T., Shirouzu M., Ogata H., Tokuyama K., Ueki K., Nagano T., Tanaka A., Yokoyama S., Kadowaki T. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013;503(7477):493-9. doi: 10.1038/nature12656.Okada-Iwabu M., Yamauchi T., Iwabu M., Honma T., Hamagami K., Matsuda K., Yamaguchi M., Tanabe H., Kimura-Someya T., Shirouzu M., Ogata H., Tokuyama K., Ueki K., Nagano T., Tanaka A., Yokoyama S., Kadowaki T. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013;503(7477):493-9. doi: 10.1038/nature12656.Iwabu M., Okada-Iwabu M., Tanabe H., Ohuchi N., Miyata K., Kobori T., Odawara S., Kadowaki Y., Yokoyama S., Yamauchi T., Kadowaki T. AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice. Commun Biol. 2021;4(1):45. doi: 10.1038/s42003-020-01579-9.Iwabu M., Okada-Iwabu M., Tanabe H., Ohuchi N., Miyata K., Kobori T., Odawara S., Kadowaki Y., Yokoyama S., Yamauchi T., Kadowaki T. AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice. Commun Biol. 2021;4(1):45. doi: 10.1038/s42003-020-01579-9.Zhang Y., Zhao J., Li R., Lau W.B., Yuan Y.X., Liang B., Li R., Gao E.H., Koch W.J., Ma X.L., Wang Y.J. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings. Am J Physiol Endocrinol Metab. 2015;309(3):E275-82. doi: 10.1152/ajpendo.00577.2014.Zhang Y., Zhao J., Li R., Lau W.B., Yuan Y.X., Liang B., Li R., Gao E.H., Koch W.J., Ma X.L., Wang Y.J. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings. Am J Physiol Endocrinol Metab. 2015;309(3):E275-82. doi: 10.1152/ajpendo.00577.2014.Clain J., Couret D., Planesse C., Krejbich-Trotot P., Meilhac O., Lefebvre d’Hellencourt C., Viranaicken W., Diotel N. Distribution of Adiponectin Receptors in the Brain of Adult Mouse: Effect of a Single Dose of the Adiponectin Receptor Agonist, AdipoRON, on Ischemic Stroke. Brain Sciences. 2022;12(5):680. https://doi.org/10.3390/brainsci12050680Clain J., Couret D., Planesse C., Krejbich-Trotot P., Meilhac O., Lefebvre d’Hellencourt C., Viranaicken W., Diotel N. Distribution of Adiponectin Receptors in the Brain of Adult Mouse: Effect of a Single Dose of the Adiponectin Receptor Agonist, AdipoRON, on Ischemic Stroke. Brain Sciences. 2022;12(5):680. https://doi.org/10.3390/brainsci12050680Herder C., Peltonen M., Svensson P.A., Carstensen M., Jacobson P., Roden M., Sjöström L., Carlsson L. Adiponectin and bariatric surgery: associations with diabetes and cardiovascular disease in the Swedish Obese Subjects Study. Diabetes Care. 2014;37(5):1401-9. doi: 10.2337/dc13-1362.Herder C., Peltonen M., Svensson P.A., Carstensen M., Jacobson P., Roden M., Sjöström L., Carlsson L. Adiponectin and bariatric surgery: associations with diabetes and cardiovascular disease in the Swedish Obese Subjects Study. Diabetes Care. 2014;37(5):1401-9. doi: 10.2337/dc13-1362.Ohashi T., Shibata R., Morimoto T., Kanashiro M., Ishii H., Ichimiya S., Hiro T., Miyauchi K., Nakagawa Y., Yamagishi M., Ozaki Y., Kimura T., Daida H., Murohara T., Matsuzaki M. Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: subgroup analysis of JAPAN-ACS study. Atherosclerosis. 2010;212(1):237-42. doi: 10.1016/j.atherosclerosis.2010.05.005.sOhashi T., Shibata R., Morimoto T., Kanashiro M., Ishii H., Ichimiya S., Hiro T., Miyauchi K., Nakagawa Y., Yamagishi M., Ozaki Y., Kimura T., Daida H., Murohara T., Matsuzaki M. Correlation between circulating adiponectin levels and coronary plaque regression during aggressive lipid-lowering therapy in patients with acute coronary syndrome: subgroup analysis of JAPAN-ACS study. Atherosclerosis. 2010;212(1):237-42. doi: 10.1016/j.atherosclerosis.2010.05.005.sGastaldelli A., Sabatini S., Carli F., Gaggini M., Bril F., Belfort-DeAguiar R., Positano V., Barb D., Kadiyala S., Harrison S., Cusi K. PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH. Liver Int. 2021;41(11):2659-2670. doi: 10.1111/liv.15005.Gastaldelli A., Sabatini S., Carli F., Gaggini M., Bril F., Belfort-DeAguiar R., Positano V., Barb D., Kadiyala S., Harrison S., Cusi K. PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH. Liver Int. 2021;41(11):2659-2670. doi: 10.1111/liv.15005.Nezu U., Tsunoda S., Yoshimura H., Kuwabara T., Tomura S., Seki Y., Kaneshiro M., Kamiyama H., Harada Y., Shigematsu E., Aoki K., Yamakawa T., Ohshige K., Natsumeda Y., Terauchi Y. Pravastatin potentiates increases in serum adiponectin concentration in dyslipidemic patients receiving thiazolidinedione: the DOLPHIN study. J Atheroscler Thromb. 2010;17(10):1063-9. doi: 10.5551/jat.5033.Nezu U., Tsunoda S., Yoshimura H., Kuwabara T., Tomura S., Seki Y., Kaneshiro M., Kamiyama H., Harada Y., Shigematsu E., Aoki K., Yamakawa T., Ohshige K., Natsumeda Y., Terauchi Y. Pravastatin potentiates increases in serum adiponectin concentration in dyslipidemic patients receiving thiazolidinedione: the DOLPHIN study. J Atheroscler Thromb. 2010;17(10):1063-9. doi: 10.5551/jat.5033.Li M., Xu A., Lam K.S., Cheung B.M., Tse H.F. Impact of combination therapy with amlodipine and atorvastatin on plasma adiponectin levels in hypertensive patients with coronary artery disease: combination therapy and adiponectin. Postgrad Med. 2011;123(6):66-71. doi: 10.3810/pgm.2011.11.2496.Li M., Xu A., Lam K.S., Cheung B.M., Tse H.F. Impact of combination therapy with amlodipine and atorvastatin on plasma adiponectin levels in hypertensive patients with coronary artery disease: combination therapy and adiponectin. Postgrad Med. 2011;123(6):66-71. doi: 10.3810/pgm.2011.11.2496.Jin H., Liu Y., Schweikert B., Hahman H., Wang L., Imhof A., Muche R., König W., Steinacker J.M. Serial Changes in Exercise Capacity, NT-proBNP, and Adiponectin in Patients with Acute Coronary Syndrome before and after Phase II Rehabilitation as well as at the 12-Month Follow-Up. Cardiol Res Pract. 2022;2022:6538296. doi: 10.1155/2022/6538296.Jin H., Liu Y., Schweikert B., Hahman H., Wang L., Imhof A., Muche R., König W., Steinacker J.M. Serial Changes in Exercise Capacity, NT-proBNP, and Adiponectin in Patients with Acute Coronary Syndrome before and after Phase II Rehabilitation as well as at the 12-Month Follow-Up. Cardiol Res Pract. 2022;2022:6538296. doi: 10.1155/2022/6538296.Фирова Э.М., Танянский Д.А. Адипонектин плазмы как предиктор эффективности терапии ишемической болезни сердца у пациентов с метаболическим синдромом. Обзоры по клинической фармакологии и лекарственной терапии. 2023;21(2):179-189. doi: 10.17816/RCF321745Firova E.M., Tanyanskiy D.A. Plasma adiponectin as a predictor of the effectiveness of coronary heart disease therapy in patients with metabolic syndrome. Reviews on Clinical Pharmacology and Drug Therapy. 2023;21(2):179-189. (In Russ.). doi: 10.17816/RCF321745Ishida M., Shimabukuro M., Yagi S., Nishimoto S., Kozuka C., Fukuda D., Soeki T., Masuzaki H., Tsutsui M., Sata M. MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism. PLoS One. 2014;9(11):e111537. doi: 10.1371/journal.pone.0111537.Ishida M., Shimabukuro M., Yagi S., Nishimoto S., Kozuka C., Fukuda D., Soeki T., Masuzaki H., Tsutsui M., Sata M. MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism. PLoS One. 2014;9(11):e111537. doi: 10.1371/journal.pone.0111537.

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