Little is known about the role of integrin-mediated mechanoelectrical coupling in cardiac myocytes. The proposed research project is designed to elucidate the role of integrin/focal adhesion kinase (FAK) signaling in stretch- and chemically- mediated up-regulation of Cx43 in neonatal rat ventricular myocytes. I will also test the hypothesis that myocyte structure and function is partly determined by interactions between myocytes and specific extracellular matrix (ECM) proteins.
In Specific Aim 1, I will characterize the levels and patterns of Cx43 expression in myocytes grown on different ECM proteins with and without uni-directional pulsatile stretch.
In Specific Aim 2, I will determine whether integrin-mediated FAK activation contributes to stretch-induced up-regulation of Cx43 in myocytes.
In Specific Aim 3, I will determine if vascular endothelial growth factor (VEGF) acts downstream of FAK in stretch-mediated up-regulation of Cx43 in myocytes.
In Specific Aim 4, I will determine if chemical mediators of stretch (VEGF, Angiotensin II) alter levels and patterns of integrin expression in myocytes. The results of the proposed studies will provide new insights into mechanisms regulating intercellular coupling and conduction in cardiac hypertrophy. ? ? ?
| Shanker, Amit J; Yamada, Kiyomi; Green, Karen G et al. (2005) Matrix-protein-specific regulation of Cx43 expression in cardiac myocytes subjected to mechanical load. Circ Res 96:558-66 |
