Angiopoietin-like 3, also known as ANGPTL3, is a protein that in humans is encoded by the ANGPTL3 gene.[5][6]
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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-terminal coiled-coil domain, and the C-terminal fibrinogen (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]
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]
Conklin D, Gilbertson D, Taft DW, Maurer MF, Whitmore TE, Smith DL, et al. (December 1999). "Identification of a mammalian angiopoietin-related protein expressed specifically in liver". Genomics. 62 (3): 477–82. doi:10.1006/geno.1999.6041. PMID 10644446. S2CID 16567474.
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. PMID 22809513.
- 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. PMID 18279878.
- 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. PMID 18804459.
- Li C (April 2006). "Genetics and regulation of angiopoietin-like proteins 3 and 4". Current Opinion in Lipidology. 17 (2): 152–6. doi:10.1097/01.mol.0000217896.67444.05. PMID 16531751. S2CID 37001655.
- Camenisch G, Pisabarro MT, Sherman D, Kowalski J, Nagel M, Hass P, et al. (May 2002). "ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo". The Journal of Biological Chemistry. 277 (19): 17281–90. doi:10.1074/jbc.M109768200. PMID 11877390.
- Kaplan R, Zhang T, Hernandez M, Gan FX, Wright SD, Waters MG, Cai TQ (January 2003). "Regulation of the angiopoietin-like protein 3 gene by LXR". Journal of Lipid Research. 44 (1): 136–43. doi:10.1194/jlr.M200367-JLR200. PMID 12518032.
- 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. PMID 12565906.
- Zeng L, Dai J, Ying K, Zhao E, Jin W, Ye Y, et al. (2003). "Identification of a novel human angiopoietin-like gene expressed mainly in heart". Journal of Human Genetics. 48 (3): 159–62. doi:10.1007/s100380300025. PMID 12624729.
- Ono M, Shimizugawa T, Shimamura M, Yoshida K, Noji-Sakikawa C, Ando Y, et al. (October 2003). "Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo". The Journal of Biological Chemistry. 278 (43): 41804–9. doi:10.1074/jbc.M302861200. PMID 12909640.
- Zhang Z, Henzel WJ (October 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
- Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
- Shimamura M, Matsuda M, Yasumo H, Okazaki M, Fujimoto K, Kono K, et al. (February 2007). "Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase". Arteriosclerosis, Thrombosis, and Vascular Biology. 27 (2): 366–72. doi:10.1161/01.ATV.0000252827.51626.89. PMID 17110602.