Persistence of the nitric oxide pathway in the aorta of hypercholesterolemic apolipoprotein-E-deficient mice.
The markers of the bioavailability of NO (endothelium-dependent relaxation to acetylcholine and cyclic GMP content) in the thoracic aorta of apolipoprotein-E-deficient (ApoE KO) mice, 20 weeks old with enriched cholesterol diet or 35 weeks old on regular chow, are not decreased, in contrast with other models of atherosclerosis. However, severe hypercholesterolemia, the presence of atherosclerotic lesions and increased NADPH oxidase activity have been reported as early as at 20 weeks of age. The present experiments were designed to test if an increased capacity of NO production in these mice explains this paradox. The expressions of the 3 isoforms of NO synthase (NOS) were compared in ApoE KO and C57Bl/6J mice using Western blot and localized by immunohistochemistry. No adaptive increase in the expression of NOS was detected in ApoE KO mice. NO bioavailability could also be preserved by upregulation of enzymes involved in redox status such as CuZn or Mn superoxide dismutase and catalase. However, these enzymes were less expressed in ApoE KO mice than in control mice. These results highlight that ApoE KO mice represent an atypical model of atherosclerosis.
Villeneuve
Nicole
N
Division Pathologies Cardiovasculaires, Institut de Recherches Servier, Suresnes, France. nicole.villeneuve@fr.netgrs.com
Fortuno
Ana
A
Sauvage
Marie
M
Fournier
Nancy
N
Breugnot
Christine
C
Jacquemin
Christine
C
Petit
Christine
C
Gosgnach
Willy
W
Carpentier
Nathalie
N
Vanhoutte
Paul
P
Vilaine
Jean-Paul
JP
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase