Inhibition or loss of function of ANGPTL3 reduces plasma levels of triglycerides, LDL-C, and HDL-C, highlighting anti-ANGPTL3 therapies as a potential strategy for treating dyslipidemia and ASCVDs.
ANGPTL3 inhibition represents a promising therapeutic strategy for managing dyslipidemia and reducing the risk of atherosclerotic cardiovascular disease.
Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein lipase (LPL) activity. Genetic, biochemical, and clinical studies in animals and humans have shown that loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events. Therefore, ANGPTL3 is considered an alternative target for lipid-lowering therapy. Emerging studies have focused on ANGPTL3 inhibition via antisense oligonucleotides (ASOs) and monoclonal antibody-based therapies, which have been carried out in mouse or monkey models and in human clinical studies for the management of dyslipidemia and ASCVDs. This review will summarize the current literature on the important role of ANGPTL3 in controlling lipoprotein metabolism and dyslipidemia, with an emphasis on anti-ANGPTL3 therapies as a potential strategy for the treatment of dyslipidemia and ASCVDs.
Chen et al. (Wed,) conducted a review in Dyslipidemia and ASCVDs. anti-ANGPTL3 therapies was evaluated. Inhibition or loss of function of ANGPTL3 reduces plasma levels of triglycerides, LDL-C, and HDL-C, highlighting anti-ANGPTL3 therapies as a potential strategy for treating dyslipidemia and ASCVDs.