Title: Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia
Authors: Patrizia Tarugi1, Stefano Bertolini2, Sebastiano Calandra3
Institutions: 1Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy; 2Department of Internal Medicine, University of Genova, Genova 16148, Italy; 3Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
Abstract: Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function (LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia (FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.
Keywords: angiopoietin-like protein 3, ANGPTL3 deficiency, loss of function variants, FHBL2
Full Text: JBR-2017-0114.pdfJBR-2017-0114-supplementary.pdf
J Biomed Res published on 10 February 2018, https://doi.org/10.7555/JBR.32.20170114