2026-06-14T12:12:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/79722024-09-27T08:27:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Lopez-Olaneta, Marina
author
Villalba-Orero, Maria
author
Gomez-Salinero, Jesus M.
author
Jimenez-Borreguero, Luis J.
author
Breckenridge, Ross
author
Ortiz-Sanchez, Paula
author
García-Pavía, Pablo
author
Ibáñez, Borja
author
Lara-Pezzi, Enrique
funder
Unión Europea. Comisión Europea
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
funder
Ministerio de Economía y Competitividad (España)
2019-07-29T07:11:27Z
2019-07-29T07:11:27Z
2014-06
Cardiovasc Res. 2014; 102(3):396-406
10.1093/cvr/cvu068
1755-3245
1755-3245
Cardiovascular research
24667850
http://hdl.handle.net/20.500.12105/7972
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, CnAβ1, 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 CnAβ1 overexpression post-infarction. METHODS AND RESULTS: Double transgenic mice with inducible cardiomyocyte-specific overexpression of CnAβ1 underwent left coronary artery ligation followed by reperfusion. Echocardiographic analysis showed depressed cardiac function in all infarcted mice 3 days post-infarction. Induction of CnAβ1 overexpression 1 week after infarction improved function and reduced ventricular dilatation. CnAβ1-overexpressing mice showed shorter, thicker scars, and reduced infarct expansion, accompanied by reduced myocardial remodelling. CnAβ1 induced vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which resulted in increased infarct vascularization. This paracrine angiogenic effect of CnAβ1 was mediated by activation of the Akt/mammalian target of rapamycin pathway and VEGF. CONCLUSIONS: Our results indicate that CnAβ1 exerts beneficial effects on the infarcted heart by promoting infarct vascularization and preventing infarct expansion. These findings emphasize the translational potential of CnAβ1 for gene-based therapies.
eng
Akt
Calcineurin
Cardiac remodelling
CnAβ1
Myocardial infarction
Induction of the calcineurin variant CnAβ1 after myocardial infarction reduces post-infarction ventricular remodelling by promoting infarct vascularization
journal article
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InductionCalcineurinVariantCnAbeta1_2014.pdf.txt