Expression of CD40 in vascular smooth muscle cells and macrophages is associated with early development of human atherosclerotic lesions

CD40-CD154-mediated signaling has recently been described as playing a role in cellular functions involved in atherosclerotic processes. CD40 is expre ssed in macrophages, lymphocytes, endothelial cells, and vascular smooth mu scle cells. However, cross-sectional studies investigating the expression o f CD40 in atherosclerotic lesions are lacking. In the present study the exp ression of CD40 was studied in atherosclerotic lesions from 43 patients cla ssified according to the World Health Organization criteria. Serial immunoh istologic stainings of human iliac arteries from 43 patients were performed using monoclonal antibodies. Lesions were classified according to World He alth Organization criteria, and CD40 expression was analyzed with regard to cell morphology and cellular markers by 2 independent observers. Human ath erosclerotic lesions revealed a significant increase in intimal thickness, number of inflammatory infiltrates, and CD40-positive macrophages and vascu lar smooth muscle cells with progression of the lesions. This increase was most prominent from stage 0 to stage 1. A significant correlation between i ntimal thickness and CD40-positive macrophages (r = 0.75, p <0.0005) and CD 40-positive vascular smooth muscle cells (r = 0.81, p <0.0005) was observed . Ligation of the cellular CD40 receptor contributes to inflammatory cellul ar events in human vascular smooth muscle cells. These data suggest a direc t association of CD40 expression in atherosclerotic lesions with early plaq ue development. (C) 2001 by Excerpta Medico, Inc.