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Genetic Deletion of NADPH Oxidase 1 Rescues Microvascular Function in Mice With Metabolic Disease

Genetic Deletion of NADPH Oxidase 1 Rescues Microvascular Function in Mice With Metabolic Disease

Authors :
David W. Stepp
Eric J. Belin de Chantemèle
Jennifer A. Thompson
Sebastian Larion
David J. Fulton
James D. Mintz
Source :
Circulation Research. 121:502-511
Publication Year :
2017
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2017.

Abstract

Rationale: Early vascular changes in metabolic disease that precipitate the development of cardiovascular complications are largely driven by reactive oxygen species accumulation, yet the extent to which excess reactive oxygen species derive from specific NADPH oxidase isoforms remains ill defined. Objective: Identify the role of Nox1 in the development of microvascular dysfunction in metabolic disease. Methods and Results: Four genotypes were generated by breeding Nox1 knockout mice with db/db mice: lean (H db W nox1 ), lean Nox1 knockout (H db K nox1 ), obese (K db W nox1 ), and obese KK (K db K nox1 ). The degree of adiposity, insulin resistance, and dyslipidemia in KW mice was not influenced by Nox1 deletion as determined by nuclear magnetic resonance spectroscopy, glucose tolerance tests, and plasma analyses. Endothelium-dependent responses to acetylcholine in pressurized mesenteric arteries were reduced in KW versus HW ( P P Conclusions: Nox1 deletion reduces oxidant load and restores microvascular health in db/db mice without influencing the degree of metabolic dysfunction. Therefore, targeted Nox1 inhibition may be effective in the prevention of vascular complications.

Details

ISSN :
15244571 and 00097330
Volume :
121
Database :
OpenAIRE
Journal :
Circulation Research
Accession number :
edsair.doi.dedup.....cde8e60bf50ce59eed8172137e32d39b
Full Text :
https://doi.org/10.1161/circresaha.116.309965