Sorafenib cardiotoxicity increases mortality after myocardial infarction
Jason M Duran1, Catherine A Makarewich1, Danielle Trappanese1
1Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA.
Circulation Research
|April 11, 2014
Summary
Sorafenib causes heart damage by killing heart cells and inhibiting stem cell repair, leading to increased mortality, especially after heart attacks. Metoprolol treatment mitigated these effects.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Sorafenib is an effective renal cell carcinoma treatment.
- Clinical reports indicate sorafenib-induced cardiotoxicity with an unknown mechanism.
Purpose of the Study:
- To determine the mechanism of sorafenib-mediated cardiotoxicity.
- Investigate sorafenib's effects on cardiac function and myocyte survival.
Main Methods:
- Mice were treated with sorafenib and underwent induced myocardial infarction (MI).
- Cardiac function was assessed via echocardiography.
- Myocyte death, stem cell apoptosis, and cardiac repair markers were analyzed.
- The effect of metoprolol co-treatment was evaluated.
Main Results:
- Sorafenib decreased survival post-MI but did not alter cardiac function.
- Sorafenib induced myocyte necrosis and apoptosis of c-kit+ stem cells.
- Smaller heart sizes and increased myocyte cross-sectional area were observed.
- Metoprolol treatment improved survival, cardiac function, and reduced myocyte loss.
Conclusions:
- Sorafenib cardiotoxicity stems from myocyte necrosis and impaired stem cell repair.
- Pathological hypertrophy occurs in surviving myocytes.
- Inhibition of c-kit+ stem cell proliferation exacerbates cardiac damage.
- Sorafenib significantly increases mortality in the context of MI.
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