Project description: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.
Project description:Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exrcise training or pathological stimuli eg pressure or volume overload. This data set looks at microRNA profiles in mouse models to examine whether phosphoinositide 3-kinase (p110 alpha isoform) activity is critical for the maintenance of cardiac function and long term survival in a seeting of heart failure (myocardial infarction). The significance and expected outcome are to recognise genes involved in models of heart failure and attempt to examine underlying regulator pathways involved in possible cardica maintenance in the PI3K mouse model. The matching mRNA gene expression profile (GSE7487) is examined to look for mRNA and microRNA interactions. miRNA expression correlates directly with cardiac function. PI3K regulon ameliorates cardiac stress. Keywords: microRNA profiling, regulatory pathway discovery, genotype comparison Ntg (non-transgenics), dnPI3K (cardiac-specific transgenic model with reduced PI3K activity) and caPI3K (transgenic mice with increased PI3K activity) mice at 3-4 months of age were used. Mice were then subjected to myocardial infarction (occlusion of the left anterior descending aorta) and sham (open heart surgery) for 8 weeks. Left ventricles were harvested. The resulting 6 experimental models were profiled accordingly. The assignment of the mouse models is as follows: caPI3K Sham, Ntg Sham, dnPI3K Sham, caPI3K MI (myocardial infarction), Ntg MI and dnPI3K MI with n = 4 in each group.
Project description:We systematically identified, annotated and characterised the mouse long non-coding transcriptome during myocardial infarction, revealing hundreds of novel heart specific lncRNAs with unique functional and regulatory characteristics.
2014-05-06 | GSE52313 | GEO
Project description:RNA-sequencing of mouse heart post myocardial infarction
Project description:A myofibroblast specific tamoxifen inducible Cre was used to assess the contribution of Yap in the mouse heart after myocardial infarction