Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque

Objective: Macrophages in atherosclerotic plaque may express the inducible isoform of NO synthase (iNOS), which produces large amounts of NO. On one h and, the production of NO can be protective by its vasodilatory, antiaggreg ant and antiproliferative effects. On the other hand, the formation of pero xynitrite from NO may favour vasospasm and thrombogenesis. In this study, w e investigated whether iNOS is present in human coronary atherosclerotic pl aque, and we correlated these data with the clinical instability of the pat ients. Methods: Fragments were retrieved by coronary atherectomy from 24 pa tients with unstable angina and 12 patients with stable angina. The presenc e of macrophages, and the production of TNF alpha, iNOS and nitrotyrosine w ere detected by immunocytochemistry. Results: Macrophage clusters were foun d in 67% of stable patients and 87% of patients with unstable angina (NS). TNF alpha was expressed in about 50% of cases in both groups, iNOS was not expressed in fragments from stable patients but was found in macrophages fr om 58% of unstable patients (P<0.001). The expression of iNOS was associate d with the presence of nitrotyrosine residues, a marker of peroxynitrite fo rmation. Expression of iNOS was correlated both with complaints of angina a t rest (P<0.05) and with the presence of thrombus at morphological examinat ion (P<0.001). Conclusion: The expression of iNOS may be induced in human c oronary atherosclerotic plaque and is associated with different factors of instability. (C) 1999 Elsevier Science B.V. All rights reserved.