Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages
Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages
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DOI：
10.1161/01.atv.19.3.646
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发表时间：
1999-03-01
影响因子：
8.7
通讯作者：
Polak, JM
中科院分区：
文献类型：
--
作者：
Baker, CSR;Hall, RJC;Polak, JM
炎症似乎在影响天然和移植冠状动脉的动脉粥样硬化病变的发展中起主要作用。随后斑块破裂和急性缺血事件的风险与炎症程度相关，并可通过阿司匹林（一种抗炎环氧合酶抑制剂）进行调节。环氧合酶-2（考克斯-2）和诱导型一氧化氮合酶（iNOS）通过前列腺素类和一氧化氮的快速和过度产生参与炎症反应，两者都可能具有促动脉粥样硬化作用。这些影响可能是介导的过氧亚硝酸盐的形成在一氧化氮的情况下，并涉及两个酶系统之间的“串扰”。本研究旨在研究自体和移植动脉粥样硬化中考克斯-2和iNOS的存在和分布。通过使用考克斯-2、iNOS和硝基酪氨酸（过氧亚硝酸盐产生的指示剂）的抗体，对患有天然（n = 12）和移植（n = 5）冠状动脉疾病的患者的动脉粥样硬化病变进行免疫细胞化学研究。对照组织取自未使用的供体心脏和尸检时的心脏。考克斯-2和iNOS在两种类型的动脉粥样硬化中主要共定位于巨噬细胞/泡沫细胞中。考克斯-2的表达也被检测到中膜平滑肌细胞和内皮细胞，包括这些血管。在巨噬细胞中，硝基酪氨酸与iNOS的分布相同，并与考克斯-2共定位。考克斯-2和iNOS在天然和移植动脉粥样硬化中共表达，可能允许酶之间的相互作用，并提示阿司匹林通过抑制考克斯-2活性而获益的另一种机制。
Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n = 12) and transplant (n = 5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, including these of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity.