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Endothelial lipase (LIPG) is a member of the triglyceride lipase gene family, primarily synthesized and secreted by vascular endothelial cells (UniProt P53657; NCBI Gene 9392). Unlike other lipases such as lipoprotein lipase or hepatic lipase, LIPG exhibits high phospholipase activity and relatively low triglyceride lipase activity, specifically targeting the phospholipids of high-density lipoprotein (HDL) particles (Jaye M, et al., 1999, Science). By hydrolyzing these phospholipids, LIPG facilitates the rapid catabolism and clearance of HDL from the circulation, thereby serving as a major negative regulator of plasma HDL-cholesterol (HDL-C) levels (Badellino KO, et al., 2006, Arterioscler Thromb Vasc Biol). Elevated expression of LIPG is clinically associated with reduced HDL-C levels and an increased risk of atherosclerosis and coronary artery disease (NCBI Gene 9392). Therapeutic strategies targeting LIPG mRNA, such as antisense oligonucleotides (ASOs), aim to reduce LIPG protein expression to elevate HDL-C levels and potentially provide cardioprotective benefits (Ionis Pharmaceuticals Pipeline).
Antisense oligonucleotide-mediated mRNA degradation
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