An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor?

Abstract

Targeting apoC-III metabolism may therefore be an important, new therapeutic approach to managing dyslipidaemia and CHD risk in obesity, insulin resistance and type 2 diabetes mellitus. However, further work is required to establish the practical aspects of measuring apoC-III in routine laboratory service and the precise therapeutic targets for serum total apoC-III and/or apoC-III in apoB-containing lipoproteins. While showing much promise as a potentially useful cardiovascular risk factor, apoC-III is not yet ready for prime time use in clinical practice.

Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes

“…*n = 8 for these values. to be enhancement of LPL activity and enhanced hepatic uptake of TRL (10,11,20). Of note, the reduction in TG noted in this study was not associated with increases in LDL-C, as often seen with TG-lowering therapies.…”

“…ApoC-III affects TG metabolism by inhibiting lipoprotein lipase (LPL) activity and by interfering with receptor-mediated uptake of TRLs by the liver (10,11). Mice overexpressing apoC-III not only have high plasma TG but also display increased insulin resistance (12).…”

Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes

“…ApoCIII is known to be an important link between glycaemia and dyslipidaemia [22] as its expression is induced by high glucose levels and is responsive to insulin. However, whilst several studies have shown that higher apoCIII content on lipoproteins is associated with their atherogenicity [23,24], the association of total circulating apoCIII itself with CVD has had less investigation [21]. One of the largest studies is the Hoorn study [25].…”

“…ApoCIII inhibits the catabolism of triacyglycerolrich lipoproteins, partly through inhibition of their hepatic uptake and partly through inhibition of lipoprotein lipase activity. ApoCIII non-specific gene deletion in animal models is associated with premature atherosclerosis [20], and most studies suggest a likely pro-atherogenic role [21]. ApoCIII is known to be an important link between glycaemia and dyslipidaemia [22] as its expression is induced by high glucose levels and is responsive to insulin.…”

LPL gene variants affect apoC-III response to combination therapy of statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia

“…ApoC-III has been associated with hypertriglyceridemia ( 19,20 ), increased cardiovascular risk ( 21 ), atherosclerosis in animal models ( 22 ), and subclinical atherosclerosis (increased coronary artery calcium) in humans ( 2 ).…”