Date of Award


Degree Type


Degree Name

Master of Science




Dr. Subrata Chakrabarti

Second Advisor

Dr. Chandan Chakraborty

Third Advisor

Dr. Zia A. Khan


Diabetic cardiomyopathy is characterized structurally by fibrosis and cardiomyocyte hypertrophy. Chronic hyperglycemia leads to increased oxidative stress and results in DNA strand breaks. This activates poly (ADP-ribose) polymerase (PARP) in an attempt to repair the damage and may also regulate transcription through transcriptional co-activator p300. We hypothesized that increased activity of PARP from oxidative stress and DNA damage may lead to transcriptional alterations and structural changes in the heart in diabetes. Two in vivo models of diabetic complications were examined utilizing two methods of PARP inhibition; genetic ablation and pharmacological inhibition with 3- aminobenzamide. The findings were confirmed in an in vitro model system. Hyperhexosemia was found to increase oxidative stress and induce cardiac hypertrophy and fibrosis. These changes were prevented with PARP inhibition. These findings elucidate, for the first time, a specific pathway involving PARP in the development of structural alterations in diabetic cardiomyopathy.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.