The cardioprotective role of renin-angiotensin system antagonists in the prevention of Bevacizumab and Sunitinib mediated cardiotoxicity
Loading...
Date
2016-10
Authors
Mozolevska, Viktoriya
Journal Title
Journal ISSN
Volume Title
Publisher
Canadian Journal of Cardiology
Abstract
Background: Targeted agents Bevacizumab and Sunitinib are associated with an increased risk of cardiovascular complications in colorectal and renal cancer settings, respectively.
Objective: To elucidate whether renin-angiotensin system (RAS) antagonists can prevent Bevacizumab and Sunitinib mediated cardiotoxicity in a murine model.
Methods: A total of 194 male mice received 0.9% saline, Bevacizumab, or Sunitinib for 4 weeks. Within each arm, daily prophylactic intake of water, Hydralazine, Aliskiren, Perindopril, or Valsartan were administered for the entire study period. Following serial hemodynamic and echocardiographic assessments, the hearts were collected for histological and biochemical analyses.
Results: Although Hydralazine effectively lowered blood pressure in Bevacizumab or Sunitinib treated mice, it was not cardioprotective. However, prophylactic administration of RAS antagonists prevented the development of hypertension, improved cardiac function, partially preserved cellular integrity, and attenuated cardiac apoptosis at week 4.
Conclusion: In a chronic murine model, RAS antagonists partially prevented Bevacizumab or Sunitinib mediated cardiotoxicity.
Description
Keywords
Cardio-oncology, Cardiotoxicity, Bevacizumab, Sunitinib, Heart failure, Renin-angiotensin system
Citation
Mozolevska V, Cheung D, Thliveris J, Singal P, Czaykowski P, Jassal DS. The art of preventing broken hearts in colorectal and renal cell cancer. Can J Cardiol. 2016 (Abstract).