Angiopoietin-like 3, also known as ANGPTL3, is a protein that in humans is encoded by the ANGPTL3gene.[5][6]
Function
The protein encoded by this gene is a member of the angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a signal peptide, N-terminalcoiled-coil domain, and the C-terminalfibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.[5]
Angptl3 also acts as dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL),[7] thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.[7]
ANGPTL3 inhibits endothelial lipase hydrolysis of HDL-phospholipid (PL), thereby increasing HDL-PL levels.[citation needed] Circulating PL-rich HDL particles have high cholesterol efflux abilities.[citation needed]
Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,[8] likely through activation by Angptl8, a feeding-induced hepatokine,[9][10] to inhibit postprandial LPL activity in cardiac and skeletal muscles,[11] as suggested by the ANGPTL3-4-8 model.[12]
Clinical significance
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.[citation needed]
In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").[13]
^Zhang R (August 2012). "Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels". Biochemical and Biophysical Research Communications. 424 (4): 786–92. doi:10.1016/j.bbrc.2012.07.038. PMID22809513.
Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, et al. (October 2008). "Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling". Atherosclerosis. 200 (2): 329–35. doi:10.1016/j.atherosclerosis.2007.12.031. PMID18279878.
Moon HD, Nakajima K, Kamiyama K, Takanashi K, Sakurabayashi I, Nagamine T (December 2008). "Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic subjects". Clinica Chimica Acta; International Journal of Clinical Chemistry. 398 (1–2): 99–104. doi:10.1016/j.cca.2008.08.021. PMID18804459.
Shimamura M, Matsuda M, Kobayashi S, Ando Y, Ono M, Koishi R, et al. (February 2003). "Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes". Biochemical and Biophysical Research Communications. 301 (2): 604–9. doi:10.1016/S0006-291X(02)03058-9. PMID12565906.
