Vascular Dendritic Cells as Gatekeepers of Lipid Accumulation Within Nascent Atherosclerotic Plaques

Abstract

See related articles, pages 383–390 Recent studies, including a series of articles coauthored by Jongstra-Bilen and Cybulsky, have brought fresh and exciting insight to the earliest stages of atherosclerotic plaque formation in mouse models of the disease. Capturing outstanding images of the lesser curvature of the murine aorta, a site highly prone to atherosclerotic plaque development, the Cybulsky laboratory revealed in 2006 that cells bearing markers of dendritic cells (DCs), including CD11c (αx integrin), take up residence just beneath the endothelium in the lesser curvature of mice.1 Possible counterparts of these DCs have also been observed in lesion-prone arterial sites of rabbits and humans.2 The initial appearance of murine DCs in the lesser curvature depends on endothelium activated in response to disturbed blood flow1,3 and is independent of plasma cholesterol status, because it occurs in standard mouse strains that are not hypercholesterolemic (Figure).1 These DCs were recently visualized in the CD11c-YFP mouse and shown to possess capacity for potent antigen presentation to T cells.4 Although they sit primarily beneath the endothelial lining, vascular DCs occasionally extend projections into the bloodstream (Figure).4 Even in the absence of hypercholesterolemia, the density of DCs within the lesser curvature of mice varies according to strain and positively correlates with the tendency of the strains to develop fulminant atherosclerosis under conditions of hypercholesterolemia.1 Moreover, the density of this population rapidly expands in the lesser curvature of low-density lipoprotein receptor (LDLR)−/− mice fed a high cholesterol diet for only a few days.1,5 Figure. Role of dendritic cells in atherosclerotic plaque development and progression. CD11c+ DCs accumulate in the subintima of plaque-prone regions in the arterial tree, even in the absence of hypercholesterolemia in a manner that is partially dependent on vascular cell …