Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease.
The oxidative modification of low-density lipoprotein (LDL) may be dependent or independent of lipid peroxidation. This peroxidation may be initiated by metal ions, possibly in association with phospholipase activity or catalyzed by myeloperoxidase independent of metal ions. It results in the generation of aldehydes, which substitute lysine residues in the apolipoprotein B-100 moiety and thus in the generation of oxidized LDL. Endothelial injury, associated with increased production of free radicals during oxidative stress, is associated with increased prostaglandin synthesis and platelet adhesion/activation. These processes are associated with the release of aldehydes, which induce the oxidative modification of LDL in the absence of lipid peroxidation and thus in the generation of malondialdehyde (MDA)-modified LDL. We have demonstrated an association between coronary artery disease (CAD) and increased plasma levels of oxidized LDL. The increase of circulating oxidized LDL is most probably independent of plaque instability. Indeed, plasma levels of oxidized LDL were very similar for patients with stable CAD and for patients with acute coronary syndromes. Acute coronary syndromes, however, were associated with increased release of MDA-modified LDL that was independent of the necrosis of myocardial cells. These data suggest that oxidized LDL is a marker of coronary atherosclerosis whereas MDA-modified LDL is a marker of plaque instability. Recently, a prospective study in cardiac transplant patients suggested an active role of oxidized LDL in the development of CAD. Oxidized LDL may contribute to the progression of atherosclerosis by enhancing endothelial injury by inducing foam cell generation and smooth muscle proliferation.
Holvoet
P
P
Center for Molecular and Vascular Biology, University of Leuven, Belgium. paulholvoet@med.kuleuven.ac.be
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D015415:Biomarkers; D008077:Lipoproteins, LDL