Abstract 317: Beta3 Integrin-mediated CTGF Expression in Cardiac Hypertrophy

Connective Tissue Growth Factor (CTGF/CCN2) is a fibrotic mediator overexpressed in human atherosclerotic lesions, myocardial infarction and hypertension. CTGF regulates ECM deposition, fibrosis, wound repair and angiogenesis. Our preliminary studies using wild type (WT) and global 3 integrin knockout (3-/-) mice show for the first time that pressure overload (PO) by transverse aortic constriction (TAC) induces both CTGF and 3 integrin expression in WT mice and that 3 integrin is a prerequisite for the PO-induced CTGF expression. Since both the major cells, cardiomyocyte (CM) and cardiac fibroblast (CFb) have been shown to express CTGF, exploring the primary source for the 3 integrin mediated CTGF expression is expected to identify potential targets for fibrosis. Therefore, the main focus of this proposed study is to use CM specific β3 integrin KO mice with preserved β3-integrin function in CFb as well as CFb specific β3 integrin KO mice with preserved β3-integrin function in CM and evaluate which heart c...