Apolipoprotein CIII

Abstract

See related articles, pages 1402–1409 The incidence of obesity-associated disorders, such as type 2 diabetes and the metabolic syndrome, is continuously increasing worldwide.1 These disorders are characterized by abnormalities in glucose and lipid metabolism, putting patients at increased risk for macro- and microvascular complications.2 Although statin treatment, which primarily targets elevated plasma low-density lipoprotein (LDL)-cholesterol levels, lowers cardiovascular morbidity and mortality in patients with type 2 diabetes,3 it is increasingly clear that a significant residual cardiovascular risk remains in these patients,3–5 which is partly attributable to the typical atherogenic lipoprotein profile (ALP) characterized by hypertriglyceridemia and low high-density lipoprotein (HDL)-cholesterol concentrations.6 Post hoc analysis of statin trials, such as PROVE-IT TIMI 22, have identified plasma triglycerides as a determinant of cardiovascular risk in patients achieving LDL-cholesterol goals.5 Plasma triglyceride concentrations are determined by the balance between clearance/uptake and production of triglyceride (TG)-rich lipoproteins (7). Dysregulation of this balance results in the development of hypertriglyceridemia.7 Triglycerides in very-low-density lipoproteins (VLDL) and chylomicrons are hydrolyzed by lipoprotein lipase, thus allowing their conversion to remnant and subsequently to LDL particles. This process is controlled by specific apolipoprotein (apo) constituents, such as apoCII and apoAV, which facilitate TG-rich lipoprotein clearance/lipolysis, whereas apoCIII delays it.8 ApoCIII is a 79-aa glycoprotein synthesized in the liver and the intestine and a major component of the apoB-containing TG-rich lipoproteins and HDL.8 Plasma apoCIII levels are positively correlated with plasma …