Purpose of review: Angiopoietin-like proteins (Angptls) comprise a family of secreted glycoproteins with high homology to angiopoietins which are important regulators of angiogenesis. Angptl3 and Angptl4 inhibit lipoprotein lipase in mice. This article reviews recent human studies on Angptls and their effects on lipoprotein profiles and cardiovascular disease.
Recent findings: Population-based studies have indicated that loss-of-function mutations of Angptl3, Angptl4, and Angptl5 are associated with a low triglyceride concentration. Angptl3 concentration is positively correlated with HDL-cholesterol, but not with triglyceride, suggesting that Angptl3 regulates HDL metabolism by inhibiting endothelial lipase. Angptl4 concentration is correlated positively with triglycerides in patients with metabolic syndrome, although most studies have failed to find such a correlation. Angptl6 has no effects on lipoprotein profiles. Angptl3 is associated with atherosclerosis in coronary, carotid, and femoral arteries. Conflicting results have been obtained regarding whether the E40K variant (a loss-of-function mutation of Angptl4) is associated with an increased risk for cardiovascular disease, which may occur due to the lipid-independent actions of Angptl4.
Summary: Angptl3, Angptl4, and possibly Angptl5 are regulators of lipoprotein metabolism in humans. Whether inhibition of these Angptls will be useful for dyslipidemia to prevent cardiovascular disease remains to be elucidated in future studies.