Impaired endothelial function is observed in several disease states that are related to obesity, such as atherosclerosis, coronary artery disease, and diabetes. Oxidative stress contributes to the development of these obesity-related diseases. NADPH oxidase is a major source of oxidative stress within the vasculature, and has been linked with the Metabolic Syndrome. However, there is no clear evidence that NADPH oxidase generated oxidative stress results in endothelial dysfunction in vivo. Furthermore, the mechanism(s) of exercise training-induced improvements in endothelial function have not been determined. The objectives of this study are to determine the impact of in vivo NADPH oxidase activity on endothelial function in obese as compared to lean individuals, and to determine the mechanism of training-induced improvements in endothelial function. Our unique microdialysis methodology will allow monitoring of microvascular/endothelial function and ROS generation, as well as the administration of pharmacological agents directly into muscle. The central hypothesis of this project is that elevated NADPH oxidase activity in obese individuals will contribute to microvascular endothelial dysfunction in skeletal muscle, and that endothelial function can be improved with a 12-week aerobic interval exercise intervention through an attenuation of NADPH oxidase activity.

Public Health Relevance

Impaired endothelial function is observed in many disease states that are related to obesity. NADPH oxidase is a major source of oxidative stress within the vasculature, and has also been linked with the metabolic syndrome and diseases associated with obesity. The purpose of this study is to investigate the impact of NADPH oxidase activity and resultant reactive oxygen species on endothelial function, and to determine if reduced NADPH oxidase activity is a mechanism of exercise training-induced improvements in endothelial function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL113854-01A1
Application #
8434433
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (90))
Program Officer
Mcdonald, Cheryl
Project Start
2013-01-17
Project End
2015-12-31
Budget Start
2013-01-17
Budget End
2015-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$435,242
Indirect Cost
$135,646
Name
East Carolina University
Department
Physiology
Type
Schools of Medicine
DUNS #
607579018
City
Greenville
State
NC
Country
United States
Zip Code
27858
La Favor, J D; Anderson, E J; Hickner, R C (2014) Novel method for detection of reactive oxygen species in vivo in human skeletal muscle. Physiol Res 63:387-92