Despite this, the activity of endothelial bound XO is increased by more than 200% in patients with CHF.36 Furthermore, studies using electron spin resonance have demonstrated that endothelial oxygen tension is thought to regulate XO activity at a post-translational level as demonstrated by a doubling in XOR activity post exposure to hypoxia without any increase in mRNA expression for 24 hours in bovine aortic endothelial cells.37 Cells produce a marked elevation in XO levels when exposed to ischemia38 and XDH conversion to XO is also accelerated in hypoxia.39 When infused acutely, XO produces a marked decrease in cardiac contractility, cardiac index and left ventricular systolic pressure.40 In atherosclerotic plaques, urate levels are found to be elevated six-fold, reflecting accelerated purine oxidation within these plaques.
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