Losartan treatment attenuates tumor-induced myocardial dysfunction

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• Cancer patients often experience fatigue and muscle wasting.
• The renin-angiotensin-aldosterone system (RAAS) and angiotensin signaling are implicated in tumor-induced muscle wasting and myocardial dysfunction.
• Angiotensin converting enzyme (ACE) inhibitors show promise in preventing chemotherapy-induced cardiovascular issues.

Purpose of the Study:

• To investigate if an angiotensin (AT) 1-receptor antagonist, Losartan, could prevent tumor-associated myocardial dysfunction.
• To assess the impact of Losartan on tumor growth, muscle mass, and systemic inflammation.

Main Methods:

• Colon26 adenocarcinoma cells were implanted in mice, with simultaneous daily administration of Losartan.
• Evaluated in vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation, systemic inflammation, and myocardial protein degradation.
• Measurements were taken 19 days post-tumor cell injection.

Main Results:

• Losartan treatment prevented tumor-induced loss of muscle mass and reduced in vitro cancer cell proliferation.
• Tumor weight was decreased, and myocardial expression of interleukin-6 was attenuated by Losartan.
• Losartan mitigated tumor-associated alterations in cardiomyocyte calcium signaling, improving myocyte contraction velocity, systolic function, and blood pressure.

Conclusions:

• Losartan effectively mitigated tumor-induced myocardial dysfunction and inflammation in a preclinical model.
• These findings suggest Losartan's potential as a therapeutic agent against cancer-related cardiac complications.