Adiponectin in normal and atherosclerotic intima of human aorta

Abstract

Adiponectin (AN) is a protein synthesized by adipocytes that has regulatory effects on lipid and lipoprotein metabolism, increases tissue sensitivity to insulin, and modulates endothelial functions and inflammatory response. However, its involvement in the processes of atherogenesis remains poorly understood. To determine the localization and sources of AN in atherosclerotic and normal human aortic intima. Immunohistochemical study was performed on sections of atherosclerotic and normal human aorta obtained during autopsy. Reverse transcription real-time PCR was performed using biopsies of para-aortic and abdominal adipose tissue, intima-media of the thoracic aorta, atherosclerotic plaques of the human carotid and femoral arteries, as well as on endothelial cells isolated from the human thoracic aorta. Transendothelial transport of AN was evaluated in a two-chamber model using a monolayer of human endothelial cell hybridoma EA.Hy926. It has been established that AN is present in atherosclerotic but not in normal human aortic intima. At the same time, AN ADIPOQ mRNA was not detected either in the intima media of the human aorta, nor in isolated endothelial cells of the aorta, nor in cells of atherosclerotic plaques of the carotid and femoral arteries. AN slowly penetrated the endothelial monolayer in vitro, but this transport was significantly enhanced by the action of tumor necrosis factor-alpha (TNFa). Obtained data indicate that AN is present in atherosclerotic but not in normal aortic intima. We assume that AN is not synthesized by the cells of normal and atherosclerotic arterial walls, but permeates from the plasma. Transendothelial transport of AN, like many other plasma proteins, is activated during the development of atherosclerotic lesions, apparently under the action of pro-inflammatory cytokines, in particular, TNFα.