Inhibition of Cholesterol Absorption

摘要: General Considerations Acyl coenzyme A:cholesterol acyltransferase (ACAT), which catalyzes the intracellular formation of cholesteryl esters, plays an important role in intestinal absorption cholesterol, foam cell within arterial wall, and VLDL production liver. Two isoforms enzyme exist, ACAT1 expressed macrophages ACAT2 intestine Cholesterol is absorbed from gut exclusively unesterified form but appears lymph esterified with various long-chain unsaturated fatty acids. The responsible ACAT, a microsomal that utilizes acyl A cholesterol as substrates. ACAT inhibitors also have potential actions beyond inhibition absorption. Inhibition hepatic could reduce esters for packaging into lipoproteins, while deposition prevent cells atherosclerotic lesions (Nissen et al. 2006; Pal 2013; Rudel Farese 2006). Nevertheless, investigations knockout mice, it known not only rate-limiting pathway On normal chow, these mice absorb efficiently wild-type if were fed cholesterol-enriched diet. (Lee 2004; Repa 2004). Under physiological conditions, alternative pathways compensate deficiency (Hussain 2005). Human ACATcDNAwas cloned human macrophage cDNA library deficient line Chinese hamster ovary cells. cDNA, labeled K1, encoded integral membrane protein 550 amino acids (Chang 1993). treatment hypercholesterolemia atherosclerosis attractive target.