Sarah C W Stevens1, Markus Velten2, Dane J Youtz1, Yvonne Clark3, Runfeng Jing3, Peter J Reiser4, Sabahattin Bicer4, Raymond D Devine5, Donna O McCarthy6, Loren E Wold7. 1. Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. 2. Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhelms-University, University Medical Center, Bonn, Germany. 3. College of Nursing, The Ohio State University, Columbus, OH, USA. 4. Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA. 5. Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, USA. 6. College of Nursing, The Ohio State University, Columbus, OH, USA; College of Nursing, Marquette University, Milwaukee, WI, USA. 7. Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; College of Nursing, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA. Electronic address: Loren.Wold@osumc.edu.
Abstract
UNLABELLED: 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. METHODS AND RESULTS: 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. CONCLUSIONS: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.
UNLABELLED: Fatigue and muscle wasting are common symptoms experienced by cancerpatients. 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 cancerpatients. 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. METHODS AND RESULTS: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-bearingmice. CONCLUSIONS: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.
Authors: Julio C B Ferreira; Jose B N Moreira; Juliane C Campos; Marcelo G Pereira; Katt C Mattos; Marcele A Coelho; Patricia C Brum Journal: Life Sci Date: 2011-01-26 Impact factor: 5.037
Authors: Xavier Bosch; Montserrat Rovira; Marta Sitges; Ariadna Domènech; José T Ortiz-Pérez; Teresa M de Caralt; Manuel Morales-Ruiz; Rosario J Perea; Mariano Monzó; Jordi Esteve Journal: J Am Coll Cardiol Date: 2013-04-10 Impact factor: 24.094
Authors: Vikash P Chauhan; John D Martin; Hao Liu; Delphine A Lacorre; Saloni R Jain; Sergey V Kozin; Triantafyllos Stylianopoulos; Ahmed S Mousa; Xiaoxing Han; Pichet Adstamongkonkul; Zoran Popović; Peigen Huang; Moungi G Bawendi; Yves Boucher; Rakesh K Jain Journal: Nat Commun Date: 2013 Impact factor: 14.919
Authors: Raymond D Devine; Sabahattin Bicer; Peter J Reiser; Loren E Wold Journal: Am J Physiol Heart Circ Physiol Date: 2017-03-24 Impact factor: 4.733
Authors: Vignesh Vudatha; Teja Devarakonda; Christopher Liu; Devon C Freudenberger; Andrea N Riner; Kelly M Herremans; Jose G Trevino Journal: Cells Date: 2022-03-18 Impact factor: 6.600