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Cardiovascular Research 1999 41(2):465-472; doi:10.1016/S0008-6363(98)00304-6
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque

Christophe Deprea,*, Xavier Havauxa, Jean Renkina, Jean Louis J. Vanoverscheldea and William Wijnsb

aDivision of Cardiology, University of Louvain Medical School, Brussels, Belgium
bCardiovascular Center, OLV Ziekenhuis Aalst, Belgium

* Address for correspondence: Division of Cardiology, University of Texas Houston Medical Center, 6431 Fannin, MSB 1.608, Houston, TX 77030. Tel.: +1-713-500-6571; fax: +1-713-500-6556.

Objective: Macrophages in atherosclerotic plaque may express the inducible isoform of NO synthase (iNOS), which produces large amounts of NO. On one hand, the production of NO can be protective by its vasodilatory, antiaggregant and antiproliferative effects. On the other hand, the formation of peroxynitrite from NO may favour vasospasm and thrombogenesis. In this study, we investigated whether iNOS is present in human coronary atherosclerotic plaque, and we correlated these data with the clinical instability of the patients. Methods: Fragments were retrieved by coronary atherectomy from 24 patients with unstable angina and 12 patients with stable angina. The presence of macrophages, and the production of TNF{alpha}, iNOS and nitrotyrosine were detected by immunocytochemistry. Results: Macrophage clusters were found 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 from 58% of unstable patients (P<0.001). The expression of iNOS was associated with the presence of nitrotyrosine residues, a marker of peroxynitrite formation. Expression of iNOS was correlated both with complaints of angina at rest (P<0.05) and with the presence of thrombus at morphological examination (P<0.001). Conclusion: The expression of iNOS may be induced in human coronary atherosclerotic plaque and is associated with different factors of instability.

KEYWORDS Atherosclerosis; Cytokines; Macrophage; Nitric oxide; Unstable angina


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