Angiopoietin-like Protein 3 (ANGPTL3) is a secreted glycoprotein that is primarily expressed in the liver. Full length ANGPTL3 circulates in the plasma as do the proteolytically separated N- and C-terminal fragments containing the coiled coil domain and fibrinogen-like domains, respectively. ANGPTL3 directly inhibits lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes responsible for hydrolyzing circulating triglycerides and HDL phospholipids. It promotes an increase in circulating triglyceride levels without altering VLDL or HDL secretion or uptake. ANGPTL3 is upregulated by LXR agonists and downregulated by Insulin, Leptin, and agonists of TR beta or PPAR beta. Its fibrinogen-like domain interacts with Integrin alphaV beta3 to induce endothelial cell adhesion, migration, and neovascularization. ANGPTL3 also promotes the expansion of hematopoietic stem cells.
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