Abstract 341: Role of Cell-to-Cell Communication in Subendothelial Cell Functions

Abstract

In subendothelial intima of adult human aorta cells form a common three-dimensional network contacting each other with their processes. This network consists mainly of pericyte-like stellate cells and smooth muscle cells. Cellular network disintegrated in early atherosclerotic lesions, in advanced atherosclerotic plaque cells lost all contacts. We believe that integration of smooth muscle cells in the form of a common cellular network is necessary for the normal physiology of the tissue while disintegration of this network play significant role in atherosclerosis. In present study, using immunocytochemistry we have found that connexin43 (Cx43), the major protein of gap junctions, drops in atherosclerotic lesions as compared with uninvolved intima. In atherosclerotic lesions, we observed that the number of Cx43 plaques is lower on lipid-laden cells than on cells free from lipid inclusions. In primary culture, subendothelial intimal cells tend to create multicellular structures in the form of clusters. Cluster creation is accompanied by the formation of gap junctions between cells; the degree of gap junctional communication depends on the density of cells in culture. We showed that such important atherosclerosis-related processes as proliferation (DNA synthesis), fibrosis (protein synthesis) and lipidosis (accumulation of intracellular cholesterol) depend on the degree of cell-to-cell communication. Dependence of proliferation and fibrosis was bell-shaped. We have incubated cells cultured from uninvolved subendothelial intima with various forms of modified LDL causing intracellular cholesterol accumulation. After incubated with modified LDL intercellular communication dropped considerably. This suggests that intracellular lipid accumulation is a reason for decrease of gap junctions. However, latex beads decrease of gap junctions, too. Thus, not cholesterol accumulation but stimulation of phagocytosis reduces intercellular contact communication. We believe that stimulation of phagocytosis accompanied by accumulation of modified LDL in intimal cells is the cause of reduction and disruption of cell-to-cell contacts. Supported by Russian Scientific Foundation (Grant # 14-15-00112).