Free Cholesterol-Induced Cytotoxicity

摘要: Abstract A major characteristic of advanced atherosclerotic lesions is the necrotic, or lipid, core, which likely plays an important role in clinical progression these lesions. Recent data suggest that necrotic core forms primarily as a consequence macrophage foam cell necrosis. Lesional macrophages initially accumulate mostly cholesteryl esters, but contain large amounts unesterified, free, cholesterol (FC). Although there are many theories to why cells die lesions, fact high FC:phospholipid (PL) ratio cellular membranes can be toxic suggests FC-induced cytotoxicity may contribute The mechanism FC explained by disturbances membrane protein function result "stiffening" bilayer and formation intracellular crystals cause physical damage organelles. Macrophages appear respond loading fascinating adaptive response, namely induction PL biosynthesis, keeps FC:PL below levels. Studies with cultured have demonstrated failure this response leads necrosis, thus similar series events could provide explanation for development core. (Trends Cardiovasc Med 1997;7: 256–263). © 1997, Elsevier Science Inc.