Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice
Por:
A. LERIDA-VISO, A. ESTEPA-FERNANDEZ, A. MORELLA-AUCEJO, B. LOZANO-TORRES, M. ALFONSO, J. BLANDEZ, V. BISBAL, P. SEPULVEDA, A. GARCIA-FERNANDEZ, M. ORZAEZ and R. MARTINEZ-MANEZ
Publicada:
1 sep 2022
Ahead of Print:
1 jul 2022
Resumen:
Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy. Here, we demonstrate that senescence induction in the heart contributes to impaired cardiac function in mice upon DOX treatment. Concomitant elimination of senescent cells with the senolytic Navitoclax in different formulations produces a significant decrease in senescence and cardiotoxicity markers together with the restoration of the cardiac function in mice followed by echocardiography. These results evidence the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced in chemotherapy-treated patients.
Filiaciones:
A. LERIDA-VISO:
Univ Politecn Valencia UPV, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe IIS La Fe, Ave Fernando Abril Martorell 106, Valencia 46026, Spain
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
A. ESTEPA-FERNANDEZ:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
A. MORELLA-AUCEJO:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
B. LOZANO-TORRES:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
M. ALFONSO:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
J. BLANDEZ:
Univ Politecn Valencia UPV, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe IIS La Fe, Ave Fernando Abril Martorell 106, Valencia 46026, Spain
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
V. BISBAL:
Ctr Invest Principe Felipe, C Eduardo Primo Yufera 3, Valencia 46012, Spain
P. SEPULVEDA:
Inst Invest Sanitaria La Fe, Regenerat Med & Heart Transplantat Unit, Av Fernando Abril Martorell 106, Valencia 46026, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
A. GARCIA-FERNANDEZ:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
:
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
Ctr Invest Principe Felipe, C Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Univ Politecn Valencia UPV, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe IIS La Fe, Ave Fernando Abril Martorell 106, Valencia 46026, Spain
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S N, Valencia 46022, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain
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