Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions -: Colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins
Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions -: Colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins
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DOI：
10.1161/01.atv.18.2.157
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发表时间：
1998-02-01
影响因子：
8.7
通讯作者：
Ylä-Herttuala, S
中科院分区：
文献类型：
--
作者：
Luoma, JS;Strålin, P;Ylä-Herttuala, S
氧化过程在动脉粥样硬化形成中起重要作用。由于超氧阴离子和一氧化氮（NO）是血管病理学中的重要介质，我们采用原位杂交和免疫细胞化学方法，同时测定了人和兔动脉粥样硬化病变中细胞外超氧化物歧化酶（EC-SOD）和诱导型一氧化氮合酶（iNOS）的表达，我们还分析了存在于动脉壁的氧化脂蛋白和过氧亚硝酸盐修饰的蛋白作为指标的氧化损伤和可能的介质在血管病理学。在早期和晚期病变的平滑肌细胞和巨噬细胞表达EC-SOD和iNOS mRNA和蛋白。两种酶在巨噬细胞中的表达尤为显著，以酶活性测定，EC-SOD是动脉壁中主要的SOD同工酶。EC-SOD活性在高细胞兔病变中较高，但在晚期结缔组织丰富的人类病变中较低。尽管EC-SOD表达丰富，但在iNOS阳性、巨噬细胞丰富的病变中检测到氧化脂蛋白的特征性丙二醛-赖氨酸和羟基壬烯醛-赖氨酸表位以及过氧亚硝酸盐修饰蛋白的特征性硝基酪氨酸残基，因此表明丙二醛、羟基壬烯醛、结论EC-SOD、iNOS及NO与超氧阴离子的平衡在动脉粥样硬化的形成中起重要作用。EC-SOD和iNOS在病变巨噬细胞中呈高表达。动脉壁EC-SOD的高表达不仅可以防止超氧阴离子的有害作用，而且还可以保护NO活性和防止过氧亚硝酸盐的形成。动脉EC-SOD和iNOS活性的调节可以提供保护动脉免受动脉粥样硬化血管疾病的手段。
Oxidative processes play an important role in atherogenesis. Because superoxide anion and nitric oxide (NO) are important mediators in vascular pathology, we studied the expression of extracellular-superoxide dismutase (EC-SOD) and inducible nitric oxide synthase (iNOS) in human and rabbit atherosclerotic lesions by using simultaneous in situ hybridization and immunocytochemistry and EC-SOD enzyme activity measurements, We also analyzed the presence in the arterial wall of oxidized lipoproteins and peroxynitrite-modified proteins as indicators of oxidative damage and possible mediators in vascular pathology. EC-SOD and iNOS mRNA and protein were expressed in smooth muscle cells and macrophages in early and advanced lesions. The expression of both enzymes was especially prominent in macrophages, As measured by enzyme activity, EC-SOD was the major SOD isoenzyme in the arterial wall. EC-SOD activity was higher in highly cellular rabbit lesions but lower in advanced, connective tissue-rich human lesions, Despite the abundant expression of EC-SOD, malondialdehyde-lysine and hydroxynonenal-lysine epitopes characteristic of oxidized lipoproteins and nitrotyrosine residues characteristic of peroxynitrite-modified proteins were detected in iNOS-positive, macrophage-rich lesions, thus implying that malondialdehyde, hydroxynonenal, and peroxynitrite are important mediators of oxidative damage, We conclude that EC-SOD, iNOS, and the balance between NO and superoxide anion play important roles in atherogenesis. EC-SOD and iNOS are highly expressed in lesion macrophages. High EC-SOD expression in the arterial wall may be required not only to prevent deleterious effects of superoxide anion but also to preserve NO activity and prevent peroxynitrite formation, Modulation of arterial EC-SOD and iNOS activities could provide means to protect arteries against atherosclerotic vascular disease.