ANGPTL3 (F8N1Q) Rabbit Monoclonal Antibody #26533

Angiopoietin-like 3 (ANGPTL3) is a secreted protein primarily expressed in liver and a regulator of fatty acid homeostasis (1). The angiopoietin-like family contains a signal peptide, an N-terminal coiled-coil domain (CCD), a linker peptide, and a C-terminal fibrinogen-like domain (FLD). Cleavage of the CCD and FLD occurs within the linker peptide, and is required for the activity of both domains (2). ANGPTL3-CCD, in concert with ANGPTL4/ANGPTL8, increases circulating triglyceride levels by inhibiting lipoprotein lipase, a hydrolase of LDL cholesterol (2,3). ANGPTL3-CCD also directly inhibits endothelial lipase, the enzyme responsible for HDL cholesterol hydrolysis (8,9). Thus, ANGPTL3-deficient mice have low levels of plasma HDL cholesterol, a risk factor for atherosclerosis (8,9). Unlike traditional angiopoietins, ANGPTL3-FLD does not bind the Tie2 receptor (4). ANGPTL3-FLD has been demonstrated to stimulate angiogenesis in endothelial cells via binding to integrin αVβ3, and to facilitate lipolysis in adipocytes via stimulation of the PDGFRβ-BRAF-ERK pathway (4,5). ANGPTL3 is currently a therapeutic target in patients with high-LDL dyslipidaemia, and can be inhibited with the use of monoclonal antibodies or antisense nucleotides (6,7).