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 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).


CONCLUSIONS
The expression of iNOS may be induced in human coronary atherosclerotic plaque and is associated with different factors of instability.
Depre
C
C
Division of Cardiology, University of Louvain Medical School, Brussels, Belgium.
Havaux
X
X
Renkin
J
J
Vanoverschelde
J L
JL
Wijns
W
W
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000201:enzymology / Q000473:pathology; D000789:Angina, Unstable / Q000201:enzymology / Q000473:pathology; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II