REDUCED ENDOTHELIAL NITRIC-OXIDE SYNTHASE EXPRESSION AND PRODUCTION IN HUMAN ATHEROSCLEROSIS

Background-NO regulates vascular tone and structure, platelets, and mo nocytes, NO is synthesized by endothelial NO synthase (eNOS). Endothel ial dysfunction occurs in atherosclerosis. Methods and Results-With a porphyrinic microsensor, NO release was measured in atherosclerotic hu man carotid arteries and normal mammary arteries obtained during surge ry. eNOS protein expression was analyzed by immunohistochemistry. In n ormal arteries, the initial rate of NO release after stimulation with calcium ionophore A23187 (10 mu mol/L) was 0.42 +/- 0.05 (mu mol/L)/s (n=10). In contrast, the initial rate of NO release was markedly reduc ed in atherosclerotic segments, to 0.08 +/- 0.04 (mu mol/L)/s (n = 10, P<0.0001), NO peak concentration in normal arteries was 0.9 +/- 0.09 mu mol/L, (n=10) and in atherosclerotic segments, 0.1 +/- 0.03 mu mol/ L (n 10, P<0,0001). Reduced NO release in atherosclerotic segments was accompanied by marked reduction of immunoreactive eNOS in luminal end othelial cells, although specific endothelial cell markers (CD31) were present (n=13), Endothelial cells of vasa vasorum of atherosclerotic segments, however, remained positive for eNOS, as was the endothelium of normal arteries. Conclusions-In clinically relevant human atheroscl erosis, eNOS protein expression and NO release are markedly reduced. T his may be involved in the progression of atherosclerosis.