Date of Award

2006

Degree Type

Thesis

Degree Name

Master of Science

Program

Pathology

Supervisor

Dr. Subrata Chakrabarti

Second Advisor

Dr. George Cherian

Third Advisor

Dr. Rennian Wang

Abstract

Oxidative stress is involved in the pathogenesis of diabetic cardiomyopathy. The localization of CD36 and endothelial nitric oxide synthase (eNOS) to the cell membrane caveolea may provide a model for the ∞ntinuous production of oxidative stress in diabetes. We hypothesized that hyperglycemia may lead to increased oxidative stress and reduced nitric oxide bioavailability through the alteration of CD36∕eNOS axis. Analysis of the heart tissues from diabetic animals revealed transcriptional upregulation of CD36 and eNOS. These changes were associated with increased oxidative damage. Microvascular endothelial cells (MVECs) exposed to high levels of glu∞se increase CD36, eNOS, and oxidative damage. Specific inhibition of CD36 prevents glucose-induced oxidative DNA and protein damage in the MVECs. In addition, we have shown for the first time that CD36 may regulate eNOS expression. In summary, upregulation of CD36 and eNOS may lead to increased oxidative stress and reduced NO in diabetes.

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