Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels
Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels
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DOI：
10.1161/01.atv.17.11.2479
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发表时间：
1997-11-01
影响因子：
8.7
通讯作者：
Marsden, PA
中科院分区：
文献类型：
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作者：
Wilcox, JN;Subramanian, RR;Marsden, PA
动脉粥样硬化与内皮源性舒张因子生物活性降低有关。为了确定这是否是由于一氧化氮合酶 (NOS) 合成减少所致，我们使用内皮型 (ecNOS)、诱导型 (iNOS) 和神经元 (nNOS) NOS 亚型特异的探针，通过原位杂交和免疫细胞化学检查了正常和动脉粥样硬化的人体血管。在正常人主动脉、脂肪条纹和晚期动脉粥样硬化病变上的内皮细胞中检测到了 ecNOS。正常血管和动脉粥样硬化血管连续切片上 ecNOS 与血管性血友病因子相对表达的比较表明，晚期病变中表达 ecNOS 的内皮细胞数量减少。在正常血管中未检测到 iNOS 和 nNOS，但在与巨噬细胞、内皮细胞和间充质内膜细胞相关的早期和晚期病变中发现了这些亚型的广泛产生。这些数据表明，(1) 晚期动脉粥样硬化病变中内皮细胞的 ecNOS 表达缺失，(2) 在由 ecNOS、nNOS 和 iNOS 亚型组成的晚期病变中，其他细胞类型的整体 NOS 合成显着增加。我们推测动脉粥样硬化斑块中 NOS 和 NO 表达的增加可能与这些组织中的细胞死亡和坏死有关。
Atherosclerosis is associated with reduced endothelium-derived relaxing factor bioactivity. To determine whether this is due to decreased synthesis of nitric oxide synthase (NOS), we examined normal and atherosclerotic human vessels by in situ hybridization and immunocytochemistry by using probes specific for endothelial (ecNOS), inducible (iNOS), and neuronal (nNOS) NOS isoforms. ecNOS was detected in endothelial cells overlying normal human aortas, fatty streaks, and advanced atherosclerotic lesions. A comparison of the relative expression of ecNOS to von Willebrand factor on serial sections of normal and atherosclerotic vessels indicated that there was a decrease in the number of endothelial cells expressing ecNOS in advanced lesions. iNOS and nNOS were not detected in normal vessels, but widespread production of these isoforms was found in early and advanced lesions associated with macrophages, endothelial cells, and mesenchymal-appearing intimal cells. These data suggest that there is (1) a loss of ecNOS expression by endothelial cells over advanced atherosclerotic lesions and (2) a significant increase in overall NOS synthesis by other cell types in advanced lesions composed of the ecNOS, nNOS, and iNOS isoforms. We hypothesize that the increased expression of NOS and presumably NO in atherosclerotic plaques may be related to cell death and necrosis in these tissues.