title: 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.
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Charles
authors.forename: Robert C
authors.initials: RC
authors.lastname: Huebert
authors.forename: Sangjin
authors.initials: S
authors.lastname: Lee
authors.forename: Neeta
authors.initials: N
authors.lastname: Adhikari
authors.forename: Sean
authors.initials: S
authors.lastname: Polster
authors.forename: James E
authors.initials: JE
authors.lastname: Rider
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Braunlin
authors.forename: Ami
authors.initials: A
authors.lastname: Mariash
authors.forename: Maggie
authors.initials: M
authors.lastname: Robledo
authors.forename: David
authors.initials: D
authors.lastname: Schuweiler
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hall
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006321:Heart / Q000254:growth & development; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D010750:Phosphoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C425468:Spry1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains
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