Luoma J S, Ylä-Herttuala S
A.I. Virtanen Institute of Molecular Sciences, University of Kuopio, Finland.
Virchows Arch. 1999 Jun;434(6):561-8. doi: 10.1007/s004280050384.
Nitric oxide (NO) is an important regulatory agent in blood vessels. We studied the expression of inducible nitric oxide synthase (iNOS) in different types of human atherosclerotic lesions using simultaneous in situ hybridization and immunocytochemistry. Since nitric oxide and its derivates or reaction products can have both oxidative and antioxidative effects, we also studied the presence of oxidized low-density lipoproteins (ox-LDL) and peroxynitrite-modified proteins in the same lesions as indicators of oxidative damage. Twenty-seven aortic samples were studied from seven autopsies. Samples were classified microscopically as normal areas, initial lesions (type I), fatty streaks (type II), intermediate lesions (type III), atheroma (type IV), fibroatheroma lesions (type Va) and fibrotic lesions (type Vc). In normal arterial wall iNOS mRNA was expressed at a low level in smooth muscle cells (SMCs). Absence of, or a low level of, epitopes characteristic of ox-LDL was found in the normal arterial wall. The expression of iNOS mRNA and protein was induced in macrophages and SMCs in the majority of early lesions and in all advanced atherosclerotic lesions. Epitopes characteristic of ox-LDL and peroxynitrite-modified proteins tended to be colocalized in iNOS-positive lesions. We consider that iNOS and oxidative injuries may play an important part in atherogenesis.
一氧化氮(NO)是血管中的一种重要调节因子。我们使用原位杂交和免疫细胞化学同步技术,研究了诱导型一氧化氮合酶(iNOS)在不同类型人类动脉粥样硬化病变中的表达。由于一氧化氮及其衍生物或反应产物可能具有氧化和抗氧化作用,我们还研究了同一病变中氧化型低密度脂蛋白(ox-LDL)和过氧亚硝酸盐修饰蛋白的存在情况,以此作为氧化损伤的指标。我们对七例尸检获取的27个主动脉样本进行了研究。样本在显微镜下被分类为正常区域、初始病变(I型)、脂纹(II型)、中间病变(III型)、粥样瘤(IV型)、纤维粥样瘤病变(Va型)和纤维化病变(Vc型)。在正常动脉壁中,iNOS mRNA在平滑肌细胞(SMC)中低水平表达。在正常动脉壁中未发现或仅发现低水平的ox-LDL特征性表位。在大多数早期病变以及所有晚期动脉粥样硬化病变中,巨噬细胞和SMC中iNOS mRNA和蛋白的表达均被诱导。ox-LDL和过氧亚硝酸盐修饰蛋白的特征性表位往往在iNOS阳性病变中共定位。我们认为,iNOS和氧化损伤可能在动脉粥样硬化的发生发展中起重要作用。