Angiopoietin-like protein 3; Angiopoietin-like protein 4 (ANGPTL3; ANGPTL4)

Angiopoietin-like protein 3 and Angiopoietin-like protein 4 are members of the angiopoietin-like protein family. ANGPTL3 is primarily expressed in the liver and plays a crucial role in regulating plasma levels of LDL cholesterol, HDL cholesterol, and triglycerides by inhibiting lipoprotein lipase and endothelial lipase. Genetic loss of ANGPTL3 leads to familial combined hypolipidemia in humans, characterized by low lipid levels and reduced cardiovascular risk. ANGPTL4 is expressed predominantly in adipose tissue and liver, acting as a potent inhibitor of lipoprotein lipase to regulate fatty acid delivery and plasma lipid concentrations. ANGPTL4 is also important for angiogenesis, wound healing, and maintenance of vascular permeability. Both proteins function by modulating the enzymatic activity of lipoprotein lipase through noncompetitive inhibition, affecting cellular uptake of lipids and overall metabolic homeostasis. They are validated therapeutic targets for drugs aimed at lowering atherogenic lipoproteins and cardiovascular risk.

Other names

Angiopoietin-related protein 3Angiopoietin-related protein 4ARP4

Inhibition of lipoprotein lipase reduces the hydrolysis of circulating triglycerides, favoring lower plasma concentrations of atherogenic lipoproteins. Therapeutic antibodies or gene-silencing agents block the interaction or reduce levels of ANGPTL3, promoting increased activity of lipoprotein lipase and lowering LDL-C, HDL-C, and triglycerides. ANGPTL4 antibodies can prevent ANGPTL4-induced inactivation of lipoprotein lipase.