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Updated: Oct 21, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model
Amber Kempton1, Cody Justice1, Aaron Guo1
1c Internal Medicine for Kempton, Davis Heart and Lung Research Institute, The Ohio State University , Columbus , OH , USA.
Background:
In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.
Objective:
Define the in vivo role of pazopanib in the development of cardiotoxicity.
Methods:
Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG's, echocardiograms, and blood pressures were recorded. At the conclusion of the study functional parameters were again recorded, and animals were used for pathological, histological, and protein analysis.
Results:
After 2 weeks of dosing with pazopanib, the treatment group exhibited a statistically significant increase in mean arterial pressure compared to control mice (119 ± 11.7 mmHg versus 108 ± 8.2 mmHg, p = 0.049). Treatment with pazopanib led to a significant reduction in the cardiac output of mice.
Conclusion:
Our findings in mice clearly demonstrate that treatment with pazopanib leads to a significant elevation in blood pressure after 2 weeks of dosing and this persists for the duration of dosing. The continued development of the cardio-oncology field will be paramount in providing optimal oncologic care while simultaneously improving cardiac outcomes through further investigation into the mechanisms of CV toxicity.
Insights
Pazopanib, used for metastatic kidney cancer, significantly increases blood pressure and reduces cardiac output in mice. Further research is needed to understand and mitigate these cardiovascular side effects.
Area of Science:
- Cardio-oncology
- Pharmacology
- Translational research
Background:
- Pazopanib is a first-line therapy for metastatic renal cell carcinoma (mRCC).
- Pazopanib treatment is associated with cardiotoxicity, including hypertension, heart failure, and myocardial ischemia.
Purpose of the Study:
- To define the in vivo role of pazopanib in the development of cardiotoxicity.
- To investigate the cardiovascular effects of pazopanib in a murine model.
Main Methods:
- Wild-type mice were administered pazopanib orally for 42 days.
- Cardiovascular parameters (ECG, echocardiogram, blood pressure) were assessed at baseline and study conclusion.
- Pathological, histological, and protein analyses were performed post-treatment.
Main Results:
- Pazopanib treatment significantly increased mean arterial pressure after 2 weeks (119 ± 11.7 mmHg vs. 108 ± 8.2 mmHg, p=0.049).
- A significant reduction in cardiac output was observed in the pazopanib-treated group.
- Elevated blood pressure persisted throughout the dosing period.
Conclusions:
- Pazopanib administration in mice leads to sustained hypertension and reduced cardiac output.
- Understanding pazopanib-induced cardiotoxicity mechanisms is crucial for improving patient outcomes in cardio-oncology.
- Further investigation into cardiovascular toxicity is essential for optimizing cancer care and cardiac health.
