Apolipoprotein CIII links dyslipidemia with atherosclerosis.
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.
Kawakami
Akio
A
Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. kawakami.vasc@tmd.ac.jp
Yoshida
Masayuki
M
D053305:Apolipoprotein C-III / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood*; D006801:Humans; D024821:Metabolic Syndrome / Q000097:blood
D053305:Apolipoprotein C-III