Explanted vein grafts with an intact endothelium demonstrate reduced focal expression of endothelial nitric oxide synthase specific to atherosclerotic sites.
The endothelial L-arginine:nitric oxide (NO) system is fundamental to vascular function. It is becoming evident that this system is compromised in aorto-coronary vein grafts, although it is not clear how it is affected. It was postulated that the development of intimal lesions in vein grafts may be associated with reduced expression or loss of endothelial NO synthase (eNOS). The immunocytochemical localization and quantitative expression of eNOS were therefore investigated in normal human saphenous veins (n = 6) and explanted vein grafts (n = 6). The vein grafts demonstrated marked morphological changes evident as fibro-intimal hyperplasia (FIH) and focal sites of atherosclerosis, often occurring along the same length of graft. Staining for eNOS was abundantly evident in the endothelium of normal veins but revealed a differential reduction in staining intensity in vein grafts. Staining intensity measurements revealed a significant reduction (P < 0.001) in the amount of eNOS present in areas of atherosclerosis as compared with normal veins and areas of vein graft with FIH changes alone. This reduction in the relative quantity of antigen was specific to eNOS, since the endothelial markers von Willebrand factor (vWf) and CD31 showed no such variations. These data support the view that vascular activity of NO is impaired in atherosclerosis and indicate that reduced expression of eNOS, and therefore by inference lower NO production, may make an important contribution to this phenomenon.
Buttery
L D
LD
Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Chester
A H
AH
Springall
D R
DR
Borland
J A
JA
Michel
T
T
Yacoub
M H
MH
Polak
J M
JM
D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology*; D006083:Graft Occlusion, Vascular / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012501:Saphenous Vein / Q000201:enzymology / Q000473:pathology / Q000637:transplantation; D013379:Substrate Specificity
D019001:Nitric Oxide Synthase