Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation.

Background: Increased inactivation of nitric oxide by oxygen free radicals contributes to endothelial dysfunction in patients with coronary artery disease (CAD). We therefore determined the activity of extracellular superoxide dismutase (EC-SOD), the major antioxidant enzyme system of the vessel wall, and its relation to flow-dependent, endothelium-mediated dilation (FDD) in patients with CAD.
Methods and Results: SOD isoenzyme activity was determined in coronary arteries from 10 patients with CAD and 10 control subjects. In addition, endothelium-bound EC-SOD activity (eEC-SOD), released by heparin bolus injection, and FDD of the radial artery were measured in 35 patients with CAD and 15 control subjects. FDD, determined by high-resolution ultrasound, was assessed at baseline, after intra-arterial infusion of vitamin C, N-monomethyl-L-arginine, and combination of both. EC-SOD activity in coronary arteries (control subjects: 126+/-14; CAD: 63+/-11 U/mg protein; P<0.01) and eEC-SOD activity in vivo (control subjects: 14.5+/-1.1; CAD: 3.8+/-1.1 U. mL(-1). min(-1); P<0.01) were reduced in patients with CAD. Activity of eEC-SOD was positively correlated with FDD (r=0.47; P<0. 01) and negatively with the effect of the antioxidant vitamin C on FDD (r=-0.59; P<0.01). In young individuals with hypercholesterolemia, however, eEC-SOD activity was increased (21. 0+/-1.2 U. mL(-1). min(-1); n=10; P<0.05).
Conclusions: In patients with CAD, vascular EC-SOD activity is substantially reduced. The close relation between endothelium-bound EC-SOD activity and FDD suggests that reduced EC-SOD activity contributes to endothelial dysfunction in patients with CAD. In young hypercholesterolemic individuals, however, endothelium-bound EC-SOD activity is increased and may, in part, counteract impairment of endothelial function as the result of increased formation of oxygen free radicals.