[Front line of oxidized lipoproteins: role of oxidized lipoproteins in atherogenesis and cardiovascular disease risk].
Ever since oxidized low density lipoprotein (LDL) was first identified in human atherosclerotic lesions, probucol was found to suppress the development of atherosclerosis in animals, and LDL incubated with vascular cells underwent oxidative modification, the so-called oxidative modification hypothesis of atherogenesis was nurtured, and a number of significant pieces of evidence have accumulated to suggest the underlying contributions of oxidized LDL to the development of atherosclerotic diseases. Recently, oxidized LDL in blood circulation can be measured, and plasma-oxidized LDL is a well-known risk marker of cardiovascular diseases. Oxidized LDL-mediated macrophage foam cell formation is probably attributed to the lack of down-regulation of oxidized LDL receptors, but high-density lipoprotein (HDL) or apolipoprotein A1-mediated cholesterol efflux from cells is also promoted, probably by oxidized LDL. This may be why macrophage cholesterol accumulation induced by oxidized LDL does not advance unilaterally. However, such a suppressive effect of HDL may be inhibited once HDL undergoes inflammatory or oxidative modification because oxidized HDL could be dysfunctional. Remnant lipoproteins can be taken up by macrophages without oxidative modification in contrast to LDL, and remnant lipoproteins exhibit many atherogenic actions similar to oxidized LDL. However, oxidized remnant lipoproteins do not function as an effective material of foam cells. Recent papers have demonstrated that oxidized phospholipid (PL)/apolipoprotein B, playing a potential role in predicting cardiovascular diseases, correlates strongly with lipoprotein (a) [(Lp (a)] because Lp (a) is susceptible to binding to oxidized PL, and oxidized Lp (a) is also detected in human coronary atherosclerotic lesions. Although many lines of evidence support the oxidized LDL hypothesis of atherosclerosis, we face important problems to be overcome, such as the fact that oxidized lipoproteins may not be relevant to human atherosclerosis because antioxidation treatments with vitamins do not necessarily prevent human cardiovascular diseases. Oxidized LDL could play a role in the initiation of foam cell generation, but become less important in the later stages of atherosclerotic disease. Taken together, we have to keep an open mind regarding the incompletely understood pathogenesis in association with oxidized lipoproteins.
Yoshida
Hiroshi
H
Department of Laboratory Medicine, Jikei University Kashiwa Hospital, Kashiwa 277-8567, Japan. hyoshida@jikei.ac.jp
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology*; D005487:Foam Cells / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology*; D012306:Risk
D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein