The role of angiopoietin-like 3 in the metabolism of lipoproteins: therapeutic perspectives

Christos Rizos, Matilda Florentin, Moses Elisaf



Hyperlipidemia is at the cornerstone of cardiovascular disease development and progression. A number of treatment options are available for the management of increased cholesterol levels. However, some patients, especially those with familial hypercholesterolemia, do not achieve their low-density lipoprotein cholesterol target despite an aggressive treatment. Currently, the mainstay of hypolipemic treatment consists of statins, ezetimibe and more recently the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. However, novel hypolipidemic targets are constantly being researched and their efficacy and potential practical usage explored. Among them, the angiopoietin-like 3 (ANGPTL3) protein, by regulating a number of lipid homeostasis pathways as well as possibly having additional beneficial effects on carbohydrate homeostasis has piqued the interest of researchers and pharmaceutical companies. Moreover, it has been shown that loss-of-function mutations of the ANGPTL3 gene in subjects are associated with decreased cardiovascular risk without side effects. This lends credence to the hypothesis that targeting ANGPTL3 may be an attractive therapeutic option in the management of hyperlipidemia. The aim of this review is to depict the pathways in which ANGPTL3 is involved and consider the ways it could act as a therapeutic target for lipid and glucose homeostasis disorders.

Keywords: angiopoietin-like 3 protein, hypercholesterolemia, cardiovascular disease, carbohydrate homeostasis