Journal article
Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction
Arteriosclerosis, thrombosis, and vascular biology, Vol.22(12), pp.1996-2002
2002
DOI: 10.1161/01.ATV.0000041629.92741.DC
PMID: 12482825
Abstract
Objective: We tested the hypothesis that deficiency of cellular glutathione peroxidase (GPx-1) enhances susceptibility to endothelial dysfunction in mice with moderate hyperhomocysteinemia.
Methods and results: Mice that were wild type (Gpx1+/+), heterozygous (Gpx1+/-), or homozygous (Gpx1-/-) for the mutated Gpx1 allele were fed a control diet or a high-methionine diet for 17 weeks. Plasma total homocysteine was elevated in mice on the high-methionine diet compared with mice on the control diet (23+/-3 versus 6+/-0.3 micromol/L, respectively; P<0.001) and was not influenced by Gpx1 genotype. In mice fed the control diet, maximal relaxation of the aorta in response to the endothelium-dependent dilator acetylcholine (10(-5) mol/L) was similar in Gpx1+/+, Gpx1+/-, and Gpx1-/- mice, but relaxation to lower concentrations of acetylcholine was selectively impaired in Gpx1-/- mice (P<0.05 versus Gpx1+/+ mice). In mice fed the high-methionine diet, relaxation to low and high concentrations of acetylcholine was impaired in Gpx1-/- mice (maximal relaxation 73+/-6% in Gpx1-/- mice versus 90+/-2% in Gpx1+/+ mice, P<0.05). No differences in vasorelaxation to nitroprusside or papaverine were observed between Gpx1+/+ and Gpx1-/- mice fed either diet. Dihydroethidium fluorescence, a marker of superoxide, was elevated in Gpx1-/- mice fed the high-methionine diet (P<0.05 versus Gpx1+/+ mice fed the control diet).
Conclusions: These findings demonstrate that deficiency of GPx-1 exacerbates endothelial dysfunction in hyperhomocysteinemic mice and provide support for the hypothesis that hyperhomocysteinemia contributes to endothelial dysfunction through a peroxide-dependent oxidative mechanism.
Details
- Title: Subtitle
- Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction
- Creators
- Sanjana DAYAL - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, United StatesKara L BROWN - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, United StatesChristine J WEYDERT - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, United StatesLarry W OBERLEY - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, United StatesErland ARNING - Baylor Institute of Metabolic Disease, Dallas, Tex, United StatesTeodoro BOTTIGLIERI - Baylor Institute of Metabolic Disease, Dallas, Tex, United StatesFrank M FARACI - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, United StatesSteven R LENTZ - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.22(12), pp.1996-2002
- Publisher
- Lippincott; Philadelphia, PA; Hagerstown, MD
- DOI
- 10.1161/01.ATV.0000041629.92741.DC
- PMID
- 12482825
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 2002
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040236002771
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