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Cardiac-specific YAP activation improve cardiac function and survival in an experimental murine MI model

ABSTRACT: In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, we found that AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, enhanced TGFβ-signaling, and activated of components of the inflammatory response.Cardiac specific YAP activation after MI mitigated myocardial injury after MI, improved cardiac function and mouse survival. These findings suggest that therapeutic activation of hYAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. Three groups were involved in this study: sham group, AAV9:Luci+MI group and AAV9-YAP+MI group. Each group contained three biological replicates. The sham group had neither myocardial infarction nor AAV injection. The AAV9:Luci +MI(L for brief) group had myocardial infarction and injected with AAV9:Luic. The AAV9:hYAP+MI(YAP for brief) group had myocardial infarction and injected with AAV9:hYAP. 5 days after MI and AAV injection, the heart apexes were collected and the total RNA were isolated for microarray analysis.

ORGANISM(S): Mus musculus  

SUBMITTER: Qing Ma   Zhiqiang Lin  Jessica N Buck  William T Pu  Pim van Gorp  Pingzhu Zhou  Jinghai Chen  Bin Zhou  Da-zhi Wang  Alexander von Gise  Fei Gu  Jonathan G Seidman  Katryna Gouin  Allan Yau 

PROVIDER: E-GEOD-54612 | ArrayExpress | 2014-05-26



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