Temporal Dynamics in Murine Cardiac Transcriptome following Myocardial Infarction
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE308914 | GEO | 2025/12/17
REPOSITORIES: GEO
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Project description:Coronary heart disease is a main cause of death in the developed world and treatment success remains modest with high mortality rates within one year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases including heart disease. Here, we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression in a mouse model of MI. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared to controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work highlights telomerase activation as a novel therapeutic strategy to prevent heart failure after MI.
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Project description:The Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown. We compared acute post-MI gene expression in C57 and MRL hearts using microarrays and identified promising candidate biological processes underlying increased survival in the MRL. Hearts from both strains were excised at different time points before or after MI for RNA extraction and hybridization to MOE430A arrays. Baseline hearts were excised from healthy mice that had not undergone the MI procedure (day 0). Infarct tissue in this case means tissue taken from the anterior-apical region that would be the infarct region in a post-MI heart. Non-infarct covers the remainder of the LV. Post-MI hearts were excised either 1 or 5 days after MI. We had successful hybridizations for 3 replicates each of C57 day 0 infarct and non-infarct tissue (6 arrays), 4 MRL day 0 infarct and non-infarct tissue (8 arrays), 4 C57 day 1 infarct and non-infarct tissue (8 arrays), 4 MRL day 1 infarct and non-infarct tissue (8 arrays), 4 C57 day 5 infarct and non-infarct tissue (8 arrays), and 4 MRL day 5 infarct and non-infarct tissue (8 arrays).
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Project description:Closed-chest reperfused MI was induced in pigs by 90-min occlusion, followed by reperfusion of the mid LAD (day 0) and by cardiac MRI with late enhancement (LE) at day 3. At day 30 the animals received either porcine APOSEC (n=8) or placebo medium (n=8) in a randomized manner, injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60, control cardiac MRI with LE and measurements of myocardial viability via diagnostic NOGA were performed. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Percutaneous endomyocardial injections of APOSEC led to a significant (p<0.05) decrease in infarct size and in improvement of cardiac index and myocardial viability compared to medium treatment. Trend towards higher LV ejection fraction was observed in APOSEC vs. the Medium placebo group (45.4±5.9% vs 37.4±8.9%, p=0.052). Transcriptome analysis revealed significant downregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher expression of myogenic factor, Mefc2 (p<0.05) gene with downregulated caspase-3 (p<0.05) in the APOSEC-pigs. We have investigated the effects of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile.
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