by Gonzalez-Valdes, I, Hidalgo, I, Bujarrabal, A, Lara-Pezzi, E, Padron-Barthe, L, Garcia-Pavia, P, Gómez-del Arco, P, Gomez, P, Redondo, J M, Ruiz-Cabello, J M, Jimenez-Borreguero, L J, Enriquez, J A, de la Pompa, J L, Hidalgo, A and Gonzalez, S
Abstract:
Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.
Reference:
Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence. (Gonzalez-Valdes, I, Hidalgo, I, Bujarrabal, A, Lara-Pezzi, E, Padron-Barthe, L, Garcia-Pavia, P, Gómez-del Arco, P, Gomez, P, Redondo, J M, Ruiz-Cabello, J M, Jimenez-Borreguero, L J, Enriquez, J A, de la Pompa, J L, Hidalgo, A and Gonzalez, S), In Nature Communications, Nature Publishing Group, volume 6, 2015.
Bibtex Entry:
@article{GonzalezValdes:2015dha,
author = {Gonzalez-Valdes, I and Hidalgo, I and Bujarrabal, A and Lara-Pezzi, E and Padron-Barthe, L and Garcia-Pavia, P and G{'o}mez-del Arco, P and Gomez, P and Redondo, J M and Ruiz-Cabello, J M and Jimenez-Borreguero, L J and Enriquez, J A and de la Pompa, J L and Hidalgo, A and Gonzalez, S},
title = {{Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.}},
journal = {Nature Communications},
year = {2015},
volume = {6},
pages = {6473},
month = mar,
publisher = {Nature Publishing Group},
affiliation = {Stem Cell Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), E-28029 Madrid, Spain.},
doi = {10.1038/ncomms7473},
pmid = {25751743},
language = {English},
rating = {0},
date-added = {2016-10-20T07:41:17GMT},
date-modified = {2018-11-22T21:14:03GMT},
abstract = {Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.},
url = {http://www.nature.com/doifinder/10.1038/ncomms7473},
uri = {url{papers3://publication/doi/10.1038/ncomms7473}}
}