Is atherosclerosis a multifactorial disease or is it induced by a sequence of lipid peroxidation reactions

摘要: Abstract: The delivery of not only free cholesterol but also esters to cells by low-density lipoprotein (LDL) has hitherto been unstudied. Minor compounds present in mammalian-derived food include linoleate and arachidonate. Evidence is presented that these are directly incorporated into VLDL responsible for the deleterious effects atherosclerosis. Cholesterol esterified with polyunsaturated fatty acids (PUFAs) readily oxidized at PUFA residue during storage heating. Apparently, liver unable distinguish between nonoxidized incorporates latter VLDL, which transformed LDL. When this LDL transferred endothelial cells, toxic products liberated induce cell damage. Cell damage combined structural changes influence neighboring cause an influx Ca2+ ions activation phospholipases lipoxygenases, resulting production lipid hydroperoxides (LOOHs). level PUFAs generated exceeds a certain limit, lipoxygenases commit suicide, causing liberation iron ions. react LOOHs thus switch from enzymatic nonenzymatic generation peroxidation (LPO) products. Although LOO· radicals produced reactions deactivated within enzyme complex, able attack any biological compound, inducing severe LOOH molecules surface injured transfer LPO phospholipid layer bypassing lipoproteins, explaining why inflammatory diseases, such as diabetes, atherogenesis.