Kanazawa K, Kawashima S, Mikami S, Miwa Y, Hirata K, Suematsu M, Hayashi Y, Itoh H, Yokoyama M
First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.
Am J Pathol. 1996 Jun;148(6):1949-56.
Atherosclerotic arteries are well known to exhibit impaired endothelium-dependent relaxation (EDR), but the exact mechanism of this impairment remains unclear. Recently, endothelial constitutive nitric oxide synthase (ECNOS), which generates nitric oxide and mediates EDR, was cloned, and ECNOS mRNA expression was reported to be modified by various cytokines, lipoproteins, and shear stress. To investigate the expression of ECNOS mRNA and protein in atherosclerotic arteries with impaired EDR, thoracic aortas isolated from Watanabe heritable hyperlipidemic (WHHL) rabbits were examined by using in situ hybridization and immunohistochemistry. Compared with thoracic aortas from Japanese White rabbits, WHHL aortas exhibited significantly impaired EDRs, although both in situ hybridization and immunohistochemistry exhibited enhanced expression of ECNOS mRNA and protein in WHHL aortas. There was no significant relationship between expression of ECNOS mRNA and protein of endothelial cells and age of the examined WHHL aortas. These data suggest that the mechanism of impaired EDR in atherosclerotic arteries is not due to the decrease in ECNOS mRNA and protein.
众所周知，动脉粥样硬化的动脉会出现内皮依赖性舒张功能受损（EDR），但其受损的确切机制尚不清楚。最近，负责生成一氧化氮并介导EDR的内皮型一氧化氮合酶（ECNOS）被克隆出来，并且有报道称，ECNOS mRNA的表达会受到多种细胞因子、脂蛋白和剪切应力的影响。为了研究EDR受损的动脉粥样硬化动脉中ECNOS mRNA和蛋白的表达情况，我们利用原位杂交和免疫组织化学方法检测了从渡边遗传性高脂血症（WHHL）兔分离出的胸主动脉。与日本白兔的胸主动脉相比，WHHL兔的胸主动脉表现出明显受损的EDR，尽管原位杂交和免疫组织化学均显示WHHL兔胸主动脉中ECNOS mRNA和蛋白的表达增强。所检测的WHHL兔胸主动脉中，内皮细胞的ECNOS mRNA和蛋白表达与年龄之间没有显著关系。这些数据表明，动脉粥样硬化动脉中EDR受损的机制并非由于ECNOS mRNA和蛋白的减少。
