The mitogen activated protein kinase (MAPK) signaling pathway regulates multiple events leading to heart failure including ventricular remodeling, contractility, hypertrophy, apoptosis, and fibrosis. The regulation of conserved intrinsic inhibitors of this pathway is poorly understood. We recently identified an up-regulation of Sprouty1 (Spry1) in a targeted approach for novel inhibitors of the MAPK signaling pathway in failing human hearts following reverse remodeling. The goal of this study was to test the hypothesis that up-regulated expression of Spry1 in cardiac myocytes would be sufficient to inhibit ERK1/2 activation and tissue remodeling. We established a murine model with up-regulated Spry1 expression in cardiac myocytes using the alpha-myosin heavy chain promoter (α-MHC). Heart weight and cardiac myocyte morphology were unchanged in adult male α-MHC-Spry1 mice compared to control mice. Ventricular function of α-MHC-Spry1 mice was unaltered at 8 weeks or 1 year of age. These findings were consistent with the lack of an effect of Spry1 on ERK1/2 activity. In summary, targeted up-regulation of Spry1 in cardiac myocytes is not sufficient to alter cell or tissue remodeling consistent with the lack of an effect on ERK1/2 activity.
Bibliographical noteFunding Information:
Acknowledgments This work was supported by a Grant-in-Aid from the American Heart Association (JH, 06555827). We thank Dr. Lorrie Kirshenbaum at the University of Manitoba for his helpful discussions with this project, Dr. Graeme Guy at the National University of Singapore for providing the murine Sprouty1 plasmid, and Dr. William Claycomb of Louisiana State University for providing us with the HL-1 cardiac myocyte cell line.