Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels.
Atherosclerosis is associated with reduced endothelium-derived relaxing factor bioactivity. To determine whether this is due to decreased synthesis of nitric oxide synthase (NOS), we examined normal and atherosclerotic human vessels by in situ hybridization and immunocytochemistry by using probes specific for endothelial (ecNOS), inducible (iNOS), and neuronal (nNOS) NOS isoforms, ecNOS was detected in endothelial cells overlying normal human aortas, fatty streaks, and advanced atherosclerotic lesions. A comparison of the relative expression of ecNOS to von Willebrand factor on serial sections of normal and atherosclerotic vessels indicated that there was a decrease in the number of endothelial cells expressing ecNOS in advanced lesions. iNOS and nNOS were not detected in normal vessels, but widespread production of these isoforms was found in early and advanced lesions associated with macrophages, endothelial cells, and mesenchymal-appearing intimal cells. These data suggest that there is (1) a loss of ecNOS expression by endothelial cells over advanced atherosclerotic lesions and (2) a significant increase in overall NOS synthesis by other cell types in advanced lesions composed of the ecNOS, nNOS, and iNOS isoforms. We hypothesize that the increased expression of NOS and presumably NO in atherosclerotic plaques may be related to cell death and necrosis in these tissues.
Wilcox
J N
JN
Emory University, Department of Medicine, Atlanta, GA 30322, USA. medjnw@emory.edu
Subramanian
R R
RR
Sundell
C L
CL
Tracey
W R
WR
Pollock
J S
JS
Harrison
D G
DG
Marsden
P A
PA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001011:Aorta / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology*; D016893:Carotid Stenosis / Q000201:enzymology / Q000473:pathology; D002648:Child; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D014651:Vasa Vasorum / Q000201:enzymology
D007527:Isoenzymes; D019001:Nitric Oxide Synthase