Expression of inducible nitric oxide synthase in macrophages and smooth muscle cells in various types of human atherosclerotic lesions.
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.
A.I. Virtanen Institute of Molecular Sciences, University of Kuopio, Finland.
J S
JS
Luoma
S
S
Ylä-Herttuala
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000201:enzymology* / Q000209:etiology; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis*
D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II