APOC3: Triglycerides do matter

INTRODUCTION Obesity, insulin resistance, and metabolic syndrome are escalating problems in developed and developing countries. High plasma triglyceride (TG) levels are commonly encountered in clinical practice; 30% of the adult US population has a TG level above 150mg/dL. Hypertriglyceridemia is perceived to be associated with increased risk of coronary heart disease (CHD) in many epidemiological studies, however the independency of TG level as a causal risk factor in promoting cardiovascular (CV) disease has remained a matter of debate for more than 3 decades. Several mechanisms may link triglycerides to atherogenesis; (1) High very low density lipoprotein (VLDL) triglyceride output activates cholesterol ester transfer protein (CETP) which leads to triglyceride enrichment of low density lipoprotein (LDL) and the formation of small dense LDL particles which are more susceptible to oxidative modification. (2) Triglyceride enrichment of high density lipoprotein (HDL) particles makes them dysfunctional. (3) Postprandial triglycerides has been reported to induce apoptosis, and increase the expression of pro-inflammatory genes. (4) Remnant lipoprotein particles (by-products of triglyceride rich lipoproteins “TRL” hydrolysis) may interfere with the function of endothelial progenitor cells, and lead to foam cell formation in a manner analogous to modified LDL particles. (5) Liberation of free fatty acids, monoacylglycerols during TRL lipolysis could cause local injury and inflammation of vascular endothelium. APOC3 – a 79-amino acid glycoprotein that is a major component of circulating TRL – (Figure 1) has received recently increasing attention. APOC3 inhibits TRL hydrolysis and promotes pro-atherogenic responses in macrophages and endothelial cells through activation of adhesion and pro-inflammatory molecules expression, and impairment of endothelial nitric oxide production and insulin signaling