Glucose-6-phosphate dehydrogenase deficiency decreases vascular superoxide and atherosclerotic lesions in apolipoprotein E(-/-) mice.
Arterioscler Thromb Vasc Biol
; 26(4): 910-6, 2006 Apr.
Article
in En
| MEDLINE
| ID: mdl-16439706
ABSTRACT
OBJECTIVE:
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that is a major source of cellular NADPH. The purpose of this study was to examine whether G6PD deficiency affects vascular oxidants and atherosclerosis in high-fat fed apolipoprotein (apo) E(-/-) mice. METHODS ANDRESULTS:
G6PD-mutant mice whose G6PD activity was 20% of normal were crossbred with apoE(-/-) mice. Among male apoE(-/-) mice that were fed a western-type diet for 11 weeks, G6PD wild-type (E-WT), and G6PD hemizygous (E-Hemi) mice were compared. Basal blood pressure was significantly higher in E-Hemi. However, superoxide anion release, nitrotyrosine, vascular cell adhesion molecule (VCAM)-1, and inducible nitric oxide synthase immunohistochemical staining were less in E-Hemi compared with E-WT aorta. Serum cholesterol level was lower in E-Hemi, but aortic lesion area was decreased in E-Hemi even after adjusting for serum cholesterol.CONCLUSIONS:
Lower NADPH production in G6PD deficiency may result in lower NADPH oxidase-derived superoxide anion, and thus lower aortic lesion growth. The association of higher blood pressure with lower serum cholesterol levels in this mouse model is indicative of the complex effects that G6PD deficiency may have on vascular disease.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins E
/
Superoxides
/
Atherosclerosis
/
Glucosephosphate Dehydrogenase Deficiency
Limits:
Animals
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Journal subject:
ANGIOLOGIA
Year:
2006
Type:
Article
Affiliation country:
United States