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Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction.
Mozolevska, Viktoriya; Schwartz, Anna; Cheung, David; Goyal, Vineet; Shaikh, Bilal; Dingman, Bella; Kim, Esther; Mittal, Ishika; Asselin, Chantal Y; Edel, Andrea; Ravandi, Amir; Thliveris, James; Singal, Pawan K; Czaykowski, Piotr; Jassal, Davinder S.
Afiliación
  • Mozolevska V; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Schwartz A; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Cheung D; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Goyal V; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Shaikh B; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Dingman B; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Kim E; Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Mittal I; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Asselin CY; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Edel A; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Ravandi A; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Thliveris J; Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Singal PK; Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Czaykowski P; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Jassal DS; Section of Hematology/Oncology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Am J Physiol Heart Circ Physiol ; 316(3): H446-H458, 2019 03 01.
Article en En | MEDLINE | ID: mdl-30499710
ABSTRACT
Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received 1) 0.9% saline, 2) BVZ (10 mg·kg-1·wk-1), or 3) SNT (40 mg·kg-1·day-1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / Disfunción Ventricular / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Antihipertensivos / Antineoplásicos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / Disfunción Ventricular / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Antihipertensivos / Antineoplásicos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Canadá