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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
- 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.
- Subjects :
- Blood Glucose
Male
0301 basic medicine
medicine.medical_specialty
Physiology
Mice, Obese
030204 cardiovascular system & hematology
Article
Muscle, Smooth, Vascular
Mice
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Metabolic Diseases
Internal medicine
medicine
Animals
NADH, NADPH Oxidoreductases
Mesenteric arteries
Mice, Knockout
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
biology
NADPH Oxidase 1
medicine.disease
Mice, Inbred C57BL
Oxidative Stress
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
NOX1
Microvessels
Knockout mouse
cardiovascular system
biology.protein
Cardiology and Cardiovascular Medicine
Gene Deletion
Dyslipidemia
Subjects
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