Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis.
Radiother Oncol
; 111(1): 63-71, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24721545
ABSTRACT
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Lesões por Radiação
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Cardiomegalia
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Fatores de Troca do Nucleotídeo Guanina
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Coração
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Amiloidose
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article