Glucose-6-phosphate dehydrogenase deficiency decreases vascular superoxide and atherosclerotic lesions in apolipoprotein E(-/-) mice.
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.


RESULTS
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.
Matsui
Reiko
R
Evans Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. rmatsui@bu.edu
Xu
Shanqin
S
Maitland
Karlene A
KA
Mastroianni
Roberto
R
Leopold
Jane A
JA
Handy
Diane E
DE
Loscalzo
Joseph
J
Cohen
Richard A
RA
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D004036:Diet, Atherogenic; D015536:Down-Regulation; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II