Depre C, Havaux X, Renkin J, Vanoverschelde J L, Wijns W
Division of Cardiology, University of Louvain Medical School, Brussels, Belgium.
Cardiovasc Res. 1999 Feb;41(2):465-72. doi: 10.1016/s0008-6363(98)00304-6.
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.
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.
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).
The expression of iNOS may be induced in human coronary atherosclerotic plaque and is associated with different factors of instability.
动脉粥样硬化斑块中的巨噬细胞可能表达诱导型一氧化氮合酶（iNOS），其可产生大量一氧化氮。一方面，一氧化氮的产生通过其血管舒张、抗聚集和抗增殖作用具有保护作用。另一方面，一氧化氮形成过氧亚硝酸盐可能会促进血管痉挛和血栓形成。在本研究中，我们调查了人类冠状动脉粥样硬化斑块中是否存在iNOS，并将这些数据与患者的临床不稳定性相关联。
通过冠状动脉旋切术从24例不稳定型心绞痛患者和12例稳定型心绞痛患者中获取组织碎片。通过免疫细胞化学检测巨噬细胞的存在以及肿瘤坏死因子α、iNOS和硝基酪氨酸的产生。
在67%的稳定型患者和87%的不稳定型心绞痛患者中发现巨噬细胞簇（无显著性差异）。两组中约50%的病例表达肿瘤坏死因子α。稳定型患者的组织碎片中未表达iNOS，但在58%的不稳定型患者的巨噬细胞中发现了iNOS（P<0.001）。iNOS的表达与过氧亚硝酸盐形成的标志物硝基酪氨酸残基的存在相关。iNOS的表达与静息性心绞痛的主诉（P<0.05）以及形态学检查时血栓的存在（P<0.001）均相关。
iNOS的表达可能在人类冠状动脉粥样硬化斑块中被诱导，并且与不同的不稳定性因素相关。
