The cardioprotective role of renin-angiotensin system antagonists in the prevention of Bevacizumab and Sunitinib mediated cardiotoxicity
| dc.contributor.author | Mozolevska, Viktoriya | |
| dc.contributor.examiningcommittee | Dixon, Ian (Physiology and Pathophysiology) Ravandi, Amir ( Physiology and Pathophysiology) Wigle, Jeffrey (Biochemistry and Medical Genetics) | en_US |
| dc.contributor.supervisor | Jassal, Davinder (Physiology and Pathophysiology) Singal, Pawan (Physiology and Pathophysiology) | en_US |
| dc.date.accessioned | 2017-09-05T15:03:03Z | |
| dc.date.available | 2017-09-05T15:03:03Z | |
| dc.date.issued | 2016-10 | en_US |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.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. | en_US |
| dc.description.note | October 2017 | en_US |
| dc.identifier.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). | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/32419 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Canadian Journal of Cardiology | en_US |
| dc.rights | open access | en_US |
| dc.subject | Cardio-oncology | en_US |
| dc.subject | Cardiotoxicity | en_US |
| dc.subject | Bevacizumab | en_US |
| dc.subject | Sunitinib | en_US |
| dc.subject | Heart failure | en_US |
| dc.subject | Renin-angiotensin system | en_US |
| dc.title | The cardioprotective role of renin-angiotensin system antagonists in the prevention of Bevacizumab and Sunitinib mediated cardiotoxicity | en_US |
| dc.type | master thesis | en_US |
| local.subject.manitoba | yes | en_US |