| First Author | López-Olañeta MM | Year | 2014 |
| Journal | Cardiovasc Res | Volume | 102 |
| Issue | 3 | Pages | 396-406 |
| PubMed ID | 24667850 | Mgi Jnum | J:229794 |
| Mgi Id | MGI:5754468 | Doi | 10.1093/cvr/cvu068 |
| Citation | Lopez-Olaneta MM, et al. (2014) Induction of the calcineurin variant CnAbeta1 after myocardial infarction reduces post-infarction ventricular remodelling by promoting infarct vascularization. Cardiovasc Res 102(3):396-406 |
| abstractText | AIMS: Ventricular remodelling following myocardial infarction progressively leads to loss of contractile capacity and heart failure. Although calcineurin promotes maladaptive cardiac hypertrophy, we recently showed that the calcineurin splicing variant, CnAbeta1, has beneficial effects on the infarcted heart. However, whether this variant limits necrosis or improves remodelling is still unknown, precluding translation to the clinical arena. Here, we explored the effects and therapeutic potential of CnAbeta1 overexpression post-infarction. METHODS AND RESULTS: Double transgenic mice with inducible cardiomyocyte-specific overexpression of CnAbeta1 underwent left coronary artery ligation followed by reperfusion. Echocardiographic analysis showed depressed cardiac function in all infarcted mice 3 days post-infarction. Induction of CnAbeta1 overexpression 1 week after infarction improved function and reduced ventricular dilatation. CnAbeta1-overexpressing mice showed shorter, thicker scars, and reduced infarct expansion, accompanied by reduced myocardial remodelling. CnAbeta1 induced vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which resulted in increased infarct vascularization. This paracrine angiogenic effect of CnAbeta1 was mediated by activation of the Akt/mammalian target of rapamycin pathway and VEGF. CONCLUSIONS: Our results indicate that CnAbeta1 exerts beneficial effects on the infarcted heart by promoting infarct vascularization and preventing infarct expansion. These findings emphasize the translational potential of CnAbeta1 for gene-based therapies. |
