ИСТИНА

Abstract Authors: A. Balatskiy1 , A. Kapatsinskaya2 , V. Tkachuk1 , 1M.V. Lomonosov Moscow State University, Medical Research and Educational Centre - Moscow - Russian Federation , 2M.V. Lomonosov Moscow State University, Faculty of Biology - Moscow - Russian Federation , Citation: European Heart Journal ( 2018 ) 39 ( Supplement ), 390 Introduction: It is well known fact that atherosclerosis usually develops in typical sites - curvatures and bifurcations of arteries. Atherogenic factors act systemically, so there must be a special mechanism of local atherogenesis induction. Shear stress plays a great role in this process, however, there are relatively straight sections of vessels in humans in which atherosclerosis frequently occurs. We suppose that in typical sites of atherogenesis some cells affecting early stages of this process can be located. The most likely candidates for this role are pericytes - progenitor cells that form clusters under the endothelium, and have the ability to accumulate lipids. Markers of these cells include NG2 (neural glial antigen 2), PDGFRβ (beta-type platelet-derived growth factor receptor), CD146 and nestin. Population of pericytes is heterogenous, so they can be either nestin-positive or nestin-negative, also it may be difficult to distinguish pericytes from immature smooth muscle cells. Recently we demonstrated that there is a small population among progenitor cells that constantly reacts to angeotensin II - a powerful atherogenic factor. Purpose: To study vascular progenitor cells' distribution in the intima of large vessels and its response to angiotensin II. Methods: C57BL/6 mice and transgenic mice carrying the eGFP gene under the nestin promoter were used. After euthanasia aortas were isolated from the heart to the renal arteries, and then were dissected longitudinally for whole-mount immunohistochemical staining or were frozen for sectioning. Antibodies to NG2, PDGFRbeta, eGFP and CD31 were used for staining. The visualization was accomplished by a confocal microscope. NG2 and PDGFRbeta double positive cells were isolated by cell sorting. The response to angiotensin II was assessed by using Ca2+ imaging in individual cells. Results: We demonstrated that nestin-positive cells are localized in the adventitia of the aorta but they are absent in the subendothelial layer. We discovered that NG2-positive cells are located in bifurcations of the aorta and its major branches (Fig. A). Double staining showed that NG2-positive cells are also PDGFRβ-positive. These cells respond to an angiotensin II application in vitro. In whole-mount stained aortas we detected a concentric arrangement of NG2-positive cells around the ostia of small vessels (Fig. B) and on the lesser curvature of the aortic arch. Conclusions: In the subendothelial layer of the aorta and large arteries there is a population of nestin-negative, NG2 and PDGFRβ positive progenitor cells located in atherosclerosis-prone regions, including curvatures and branching sites. These cells respond to angiotensin II and may promote early stages of atherogenesis.