Adiponectin and atherosclerosis

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Abstract

The review is devoted to discussion the data regarding involvement of the adipocytes’ secreting protein, adiponectin, in atherogenesis. The questions relating the structure of its molecular forms, mechanisms of its production and signaling are also considered. Based on analysis of clinical studies and the results obtained in animals and cell cultures it is thought that adiponectin has both antiatherogenic and proatherogenic properties.

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About the authors

Dmitrii A. Tanianskii

Institute of Experimental Medicine; Saint-Petersburg State University; Pavlov First Saint-Petersburg State Medical University

Author for correspondence.
Email: dmitry.athero@gmail.com

MD, PhD, Head of the Laboratory of Lipoproteins of the Biochemistry Department

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376; 7/9, Universitetskaya embankment, Saint-Petersburg, 199034; 6/8, Lva Tolstogo street, St. Petersburg, 197089

Nina S. Parfenova

Institute of Experimental Medicine

Email: nina.parf@mail.ru

MD, PhD, Senior Research Scientist of the Laboratory of Lipoproteins of the Biochemistry Department

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Nina G. Nikulcheva

Institute of Experimental Medicine

Email: nikulcheva@mail.ru

MD, PhD, Leading research associate of the Laboratory of Lipoproteins of the Biochemistry Department

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Alexander D. Denisenko

Institute of Experimental Medicine; Saint-Petersburg State University

Email: add@iem.sp.ru

MD, PhD, Professor, Head of the Biochemistry Department

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376; 7/9, Universitetskaya embankment, Saint-Petersburg, 199034

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2. Fig. 1. Structure of molecular forms and signaling mechanisms of action of adiponectin: ACC1 - acetyl CoA carboxylase-1; AdipoR1 / R2 - adiponectin receptors types 1 and 2; AMPK - AMP-dependent protein kinase; APPL1 is an adapter protein containing a plecstrin homologous domain, a phosphotyrosine-binding domain, and a leucine zipper domain; Ca2 + - calcium ions; CaMKK - Ca2 + -calmodulin-dependent kinase kinase; eNOS - endothelial synthetase nitric oxide NO; LKB1 - hepatic kinase-1; NF-κB - transcription factor nuclear factor κB; P is the phosphorylated form of the protein; p38 - mitogen-activated protein kinase p38; PLC - phospholipase C; PPARα - nuclear receptor activated by peroxisome-α proliferators; S1P - sphingosine-1-phosphate; SphK - sphingosine kinase; Glyut-4 - glucose transporter Glyut-4

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3. Fig. 2. The effect of adiponectin on the cells of the vascular wall. The vertical fat arrows indicate the suppressive and stimulating effects of adiponectin. Adiponectin attenuates the stimulated tumor necrosis factor-α (TNFα) expression of adhesion molecules E-selectin, intercellular adhesion molecules-1 (ICAM-1), adhesion molecules of vascular endothelium-1 (VCAM-1) on the surface of endotheliocytes (E), production by these cells interleukin-8 (IL-8) chemokine, as well as TNFα-induced paracellular transport of plasma proteins through the endothelium and, presumably, low-density lipoprotein (LDL). At the same time, adiponectin increases the production of nitric oxide (NO) by endotheliocytes, which has an anti-adhesive and anti-ischemic effect. Adiponectin suppresses the uptake of oxidized LDL (okLNP) by macrophages, and also enhances the elimination of cholesterol from these cells to apolipoprotein A-1 (apo A-1) and high-density lipoproteins (HDL) by stimulating the expression of ABC-cassette ABCA-1. Adiponectin weakens lipopolysaccharide- (LPS) and TNFα-dependent differentiation of monocytes into proinflammatory macrophages (M1), thereby reducing the production of cytokines TNFα, IL-1, 12 and monocyte chemoattractant protein-1 (MCP-1), and stimulates IL-4 dependent differentiation into anti-inflammatory macrophages M2, producing IL-10. Adiponectin inhibits the activity of matrix metalloproteinases (MMP) by means of an IL-10-dependent increase in macrophage production of a tissue MMP inhibitor (TIMP), but at the same time increases the production of MMP by endothelial cells. Adiponectin inhibits the migration, proliferation and secretory transformation of vascular smooth myocytes (MMC) and increases the production of vascular endothelial growth factor (VEGF) by endotheliocytes

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Copyright (c) 2018 Tanianskii D.A., Parfenova N.S., Nikulcheva N.G., Denisenko A.D.

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