Journal article
Nox2-Derived Superoxide Contributes to Cerebral Vascular Dysfunction in Diet-Induced Obesity
Stroke (1970), Vol.44(11), pp.3195-3201
11/01/2013
DOI: 10.1161/STROKEAHA.113.001366
PMCID: PMC4011083
PMID: 24072007
Abstract
Background and Purpose Obesity is an increasing epidemic worldwide; however, little is known about effects of obesity produced by high-fat diet (HFD) on the cerebral circulation. The purpose of this study was to examine the functional and temporal effects of a HFD on carotid and cerebral vascular function and to identify mechanisms that contribute to such functional alterations.
Methods Responses of cerebral arterioles (in vivo) and carotid arteries (in vitro) were examined in C57Bl/6 (wild-type) and Nox2-deficient (Nox2(-/-)) mice fed a control (10%) or a HFD (45% or 60% kcal of fat) for 8, 12, 30, or 36 weeks.
Results In wild-type mice, a HFD produced obesity and endothelial dysfunction by 12 and 36 weeks in cerebral arterioles and carotid arteries, respectively. Endothelial function could be significantly improved with Tempol (a superoxide scavenger) treatment in wild-type mice fed a HFD. Despite producing a similar degree of obesity in both wild-type and Nox2(-/-) mice, endothelial dysfunction was observed only in wild-type, but not in Nox2(-/-), mice fed a HFD.
Conclusions Endothelial dysfunction produced by a HFD occurs in a temporal manner and appears much earlier in cerebral arterioles than in carotid arteries. Genetic studies revealed that Nox2-derived superoxide plays a major role in endothelial dysfunction produced by a HFD. Such functional changes may serve to predispose blood vessels to reduced vasodilator responses and thus may contribute to alterations in cerebral blood flow associated with obesity.
Details
- Title: Subtitle
- Nox2-Derived Superoxide Contributes to Cerebral Vascular Dysfunction in Diet-Induced Obesity
- Creators
- Cynthia M. Lynch - Roy J. and Lucille A. Carver College of MedicineDale A. Kinzenbaw - Augusta UniversityXunxheng Chen - University of Mississippi Medical CenterShanshan Zhan - Charlie Norwood VA Medical CenterErin Mezzetti - Prevention InstituteJessica Filosa - Institute of PhysiologyAdviye Ergul - Prevention InstituteJessica L. Faulkner - University of MississippiFrank M. Faraci - University of IowaSean P. Didion - University of Mississippi
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.44(11), pp.3195-3201
- DOI
- 10.1161/STROKEAHA.113.001366
- PMID
- 24072007
- PMCID
- PMC4011083
- NLM abbreviation
- Stroke
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- P01HL062984 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Georgia Health Sciences University's Diabetes and Obesity Discovery Institute HL-089884; HL-107632; NS-24621; HL-62984; HL-089067; NS-054688 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01NS024621 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) I01BX000347 / Veterans Affairs; US Department of Veterans Affairs BX000347 / Veterans Affairs Merit grant; US Department of Veterans Affairs EIA-0740002N / American Heart Association
- Language
- English
- Date published
- 11/01/2013
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984303748102771
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