Angiopoietin-like 3: An important protein in regulating lipoprotein levels

ANGPTL3 has emerged as a therapeutic target whose inhibition results in profound reductions of plasma lipids, including athero-genic triglyceride-rich lipoproteins and low-density lipoprotein cholesterol. The identification of ANGPTL3 deficiency as a cause of familial combined hypolipidemia in humans hastened the devel-opment of anti-ANGPTL3 therapeutic agents, including evinacu-mab (a monoclonal antibody inhibiting circulating ANGPTL3), vupanorsen (an antisense oligonucleotide [ASO] targeting hepatic ANGPTL3 mRNA for degradation), and others. Advances have also been made in ANGPTL3 vaccination and gene editing strategies, with the former still in preclinical phases and the latter in prep-aration for Phase 1 trials. Here, we review the discovery of ANGPTL3 as an important regulator of lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti - ANGPTL3 agents. The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

ANGPTL3 has been identified as a therapeutic target for reducing plasma lipids, including atherogenic lipoproteins and LDL cholesterol. Therapeutic agents such as evinacumab (a monoclonal antibody), vupanorsen (an antisense oligonucleotide), and others have been developed to inhibit ANGPTL3. Vaccination and gene editing strategies for ANGPTL3 are also being explored. The success of ANGPTL3 inhibition therapies underscores its importance in treating refractory hypertriglyceridemia and hypercholesterolemia.