Ox-LDL and vasoconstriction

Coronary artery spasm may account for a variety of clinical syndromes such as variant angina, acute myocardial infarction and sudden cardiac death [94]. The mechanisms of vasospasm however are not entirely clear. Atherosclerosis and hypercholesterolemia have been implicated in the pathogenesis of vasospasm [95-97] and a local hyperactivity of the coronary artery may be involved. 

Recent findings [117] suggest that native LDL and Ox-LDL directly inactivate EDRF but do not attenuate formation of EDRF in cultured and native endothelial cells after short-term exposure. A direct inactivation of EDRF by the lipoproteins rather than an effect on the target-organ smooth muscle has been involved [117]. It has been reported that contractions to native LDL are due to its oxidation in the organ chamber, and that Ox-LDL, but not native LDL, inhibits endothelium-dependent relaxations to 5HT. In fact, the native-LDL molecule is known to be unstable after its isolation from the blood, is readily auto-oxidised in the presence of air, and is highly sensitive to metal-catalyzed oxidation [118], 

Inhibitory effects of high concentrations of LDL (2000 pg/ml) on endothelium-dependent arterial relaxation have been reported by Andrews et al. [119]. These authors suggested that the effects are mediated by an apolipoprotein receptor mechanism involving native LDL. 

Therefore, arteriosclerosis arteries are more prone to vasospastic events than are normal blood vessels [98]. One feature of this disease is the impairment of the relaxations mediated by the endothelium. This endothelial abnormality appears to be partially due to a defect of the metabolism of EDRF by Ox-LDL which accumulates within human atherosclerotic plaques. However, an enhanced production of the potent vasoconstrictor peptide endothelin could also participate in vasospasm. It has been reported that Ox-LDL induces the release of endothelin from human and porcine endothelium [126,127] and from bovine endothelium [128]. 

Endothelins have been isolated, purified, and identified as 21 amino-acid peptides [129] and are the most potent vasoconstrictor molecules. Indeed, the circulating levels of endothelin are increased in hypercholesterolemic rats [130] and in human patients with hyperlipidemia or atherosclerosis [131,132], 

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