Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Pathology
Supervisor
Dr. Subrata Chakrabarti
Second Advisor
Dr. Chandan Chakraborty
Third Advisor
Dr. Zia A. Khan
Abstract
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.
Recommended Citation
Chiu, Jane, "PARP-MEDIATED STRUCTURAL ALTERATIONS IN DIABETIC CARDIOMYOPATHY" (2008). Digitized Theses. 4860.
https://ir.lib.uwo.ca/digitizedtheses/4860