NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbolmyristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology. Lipoproteininduced generation of TNF-alpha, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to bemediated through theNF-kappa Bpathway as FDreduced expression ofNF-kappa Band atherosclerosis-associated genes. Compared to controls, FDdramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization. (C) 2017 Elsevier Inc. All rights reserved.