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Targeted Sprouty1 overexpression in cardiac myocytes does not alter myocardial remodeling or function.


ABSTRACT: 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 (alpha-MHC). Heart weight and cardiac myocyte morphology were unchanged in adult male alpha-MHC-Spry1 mice compared to control mice. Ventricular function of alpha-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.

SUBMITTER: Charles NJ 

PROVIDER: S-EPMC2923832 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Targeted Sprouty1 overexpression in cardiac myocytes does not alter myocardial remodeling or function.

Charles Nathan J NJ   Huebert Robert C RC   Lee Sangjin S   Adhikari Neeta N   Polster Sean S   Rider James E JE   Braunlin Elizabeth E   Mariash Ami A   Robledo Maggie M   Schuweiler David D   Hall Jennifer L JL  

Molecular and cellular biochemistry 20100512 1-2


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 wa  ...[more]

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