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Losartan treatment attenuates tumor-induced myocardial dysfunction.

ABSTRACT: Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction.Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice.These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.

SUBMITTER: Stevens SC

PROVIDER: S-EPMC4530048 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Losartan treatment attenuates tumor-induced myocardial dysfunction.

Stevens Sarah C W SC Velten Markus M Youtz Dane J DJ Clark Yvonne Y Jing Runfeng R Reiser Peter J PJ Bicer Sabahattin S Devine Raymond D RD McCarthy Donna O DO Wold Loren E LE

Journal of molecular and cellular cardiology 20150516

<h4>Unlabelled</h4>Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role f ...[more]

PMID: 25988231

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Losartan treatment attenuates tumor-induced myocardial dysfunction.

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Losartan treatment attenuates tumor-induced myocardial dysfunction.

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