Angiotensin-(1-9) prevents cardiomyocyte hypertrophy via miR-129-3p/PKIA/PKA signaling pathway

Angiotensin-(1-9) is a peptide from the non-canonical renin-angiotensin system with anti-hypertrophic effects in cardiomyocytes via an unknown mechanism. Our previous work proved that this peptide induces mitochondrial fusion through Drp1 phosphorylation and prevented norepinephrine-elicited mitochondrial fission. In the present work, we aimed to elucidate the underlying mechanism by which angiotensin-(1-9) could prevent cardiomyocyte hypertrophy together with its effects over mitochondrial dynamics evaluating the possible link between them and the signaling pathways activated during hypertrophy. Here we show, for the first time, that angiotensin-(1-9) prevents intracellular calcium dysregulation and the activation of Calcineurin/NFAT signaling pathway at a transcription and protein level in a model of norepinephrine-induced cardiomyocyte hypertrophy. To further investigate the anti-hypertrophic mechanism of angiotensin-(1-9), we performed RNA-seq studies, identifying the upregulation of miR-129 under angiotensin-(1-9) treatment. miR-129 decreased the transcript levels of the protein kinase A inhibitor (PKIA), resulting in the activation of the protein kinase A (PKA) signaling pathway. Finally, we showed that the mere activation of PKA by angiotensin-(1-9) accounted for its effects on calcium handling and cardiomyocyte hypertrophy

Grantor dc:publisher

Universidad de Chile

Year dc:date.issued

2020

Author dc:creator

• Sotomayor Flores, Cristian Alejandro

Advisors dc:contributor.advisor

• Lavandero González, Sergio
• Corvalán Rodríguez, Alejandro Hernán
• Meister, Gunter

• Angiotensinas
• Cardiomegalia

Statement dc:rights

• Attribution-NonCommercial-NoDerivs 3.0 Chile

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/3.0/cl/

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repositorio.uchile.cl/handle/2250/178377

OAI identifier oai:identifier

oai:repositorio.uchile.cl:2250/178377