Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis.

Détails

ID Serval
serval:BIB_AF47671526E1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis.
Périodique
Radiotherapy and Oncology
Auteur⸱e⸱s
Monceau V., Llach A., Azria D., Bridier A., Petit B., Mazevet M., Strup-Perrot C., To T.H., Calmels L., Germaini M.M., Gourgou S., Fenoglietto P., Bourgier C., Gomez A.M., Escoubet B., Dörr W., Haagen J., Deutsch E., Morel E., Vozenin M.C.
ISSN
1879-0887 (Electronic)
ISSN-L
0167-8140
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
111
Numéro
1
Pages
63-71
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
BACKGROUND: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target.
METHODS: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes.
RESULTS: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals.
CONCLUSION: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.
Pubmed
Web of science
Création de la notice
05/08/2014 19:02
Dernière modification de la notice
20/08/2019 16:18
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