Plasma levels of
lipoproteins that contain
apolipoprotein (apo) CIII predict
coronary heart disease (CHD), and associate with contributors to
metabolic syndrome such as
type 2 diabetes and
hypertriglyceridemia. ApoCIII causes
hypertriglyceridemia by inhibiting the catabolism and the clearance of TG-rich
lipoproteins (TLRs), and the association of apoCIII with CHD has been commonly attributed to these properties; however, it has been untested whether apoCIII itself or in association with
lipoproteins directly affects atherogenic mechanisms in vascular cells. This review describes the proatherogenic effect of apoCIII-containing
lipoproteins. In brief, apoCIII-rich VLDL (VLDL CIII+) increased the adhesion of human monocytes to vascular endothelial cells (ECs). ApoCIII alone also increased monocyte adhesion to vascular ECs. Interestingly, apoCIII-rich HDL did not reduce the adhesion of monocytes to vascular ECs, whereas HDL without apoCIII decreased their adhesion, suggesting that apoCIII in HDL counteracts the anti-inflammatory property of HDL. ApoCIII alone as well as VLDL CIII+also activated vascular ECs through the activation of
NF-kappaB, and induced the recruitment of monocytes to vascular ECs. Moreover, apoCIII induced
insulin resistance in vascular ECs and caused endothelial dysfunction. These findings indicate that apoCIII in TLRs not only modulates their metabolism, but also may directly contribute to the development of
atherosclerosis by activating the proinflammatory signal transduction of vascular cells. Here, we propose a novel role for apoCIII that links
dyslipidemia with
atherosclerosis.