2026-04-26T23:12:00Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/98502024-09-27T09:10:43Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Martinez-Martinez, Sara
author
Lozano-Vidal, Noelia
author
Lopez-Maderuelo, Dolores
author
Jimenez-Borreguero, Luis J.
author
Armesilla, Angel Luis
author
Redondo, Juan Miguel
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Fundación ProCNIC
funder
Fundación La Marató TV3
funder
Ministerio de Sanidad y Consumo (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
2020-04-30T14:40:10Z
2020-04-30T14:40:10Z
2019-02
FEBS J. 2019; 286(1):46-65
1742-464X
http://hdl.handle.net/20.500.12105/9850
30548183
10.1111/febs.14718
1742-4658
The FEBS journal
Previous studies have demonstrated that activation of calcineurin induces pathological cardiac hypertrophy (CH). In these studies, loss-of-function was mostly achieved by systemic administration of the calcineurin inhibitor cyclosporin A. The lack of conditional knockout models for calcineurin function has impeded progress toward defining the role of this protein during the onset and the development of CH in adults. Here, we exploited a mouse model of CH based on the infusion of a hypertensive dose of angiotensin II (AngII) to model the role of calcineurin in CH in adulthood. AngII-induced CH in adult mice was reduced by treatment with cyclosporin A, without affecting the associated increase in blood pressure, and also by induction of calcineurin deletion in adult mouse cardiomyocytes, indicating that cardiomyocyte calcineurin is required for AngII-induced CH. Surprisingly, cardiac-specific deletion of calcineurin, but not treatment of mice with cyclosporin A, significantly reduced AngII-induced cardiac fibrosis and apoptosis. Analysis of profibrotic genes revealed that AngII-induced expression of Tgfβ family members and Lox was not inhibited by cyclosporin A but was markedly reduced by cardiac-specific calcineurin deletion. These results show that AngII induces a direct, calcineurin-dependent prohypertrophic effect in cardiomyocytes, as well as a systemic hypertensive effect that is independent of calcineurin activity.
eng
Angiotensin II
Cyclosporin A
Heart
Pro-fibrotic genes
Cardiomyocyte calcineurin is required for the onset and progression of cardiac hypertrophy and fibrosis in adult mice
journal article
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CardiomyocyteCalcineurinRequiredOnset_2019.pdf
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CardiomyocyteCalcineurinRequiredOnset_2019_supplementaryfigure.pdf
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CardiomyocyteCalcineurinRequiredOnset_2019.pdf.txt
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