Date of Award
2011
Degree Type
Thesis
Degree Name
Master of Science
Program
Pathology
Supervisor
Dr. Tianqing Peng
Second Advisor
Dr. Subrata Chakrabarti
Abstract
Cardiovascular complications are the leading cause of diabetes-related morbidity and mortality. Calpain, a calcium-dependent protease, is increased in diabetic hearts yet its role in diabetic heart disease has not been demonstrated. We hypothesized that inhibition of calpain activity via calpastatin (CAST) over-expression will reduce the onset of myocardial fibrosis, a hallmark of diabetic cardiomyopathy, in the Type 2 murine model, db/db. Histological analysis together with gene expression measurements showed calpastatin over-expression reduced collagen content in db/db-CAST hearts. In order to understand the mechanisms responsible for this change, fibroblasts and known mediators of collagen synthesis and degradation were studied. Results indicated that calpain-induced derangements in MMP activity, stimulation of immune cells and up- regulation of cytokines responsible for promoting fibroblast differentiation and proliferation were reversed by calpastatin over-expression. This study shows that calpain inhibition is an effective means of decreasing collagen accumulation in the diabetic heart.
Recommended Citation
Singh, Manpreet, "CALPASTATIN OVER-EXPRESSION REDUCES CARDIAC FIBROSIS IN A MURINE MODEL OF TYPE 2 DIABETES" (2011). Digitized Theses. 3283.
https://ir.lib.uwo.ca/digitizedtheses/3283