title: 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.
  
  
  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.
authors.affiliation: Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Sarah C W
authors.initials: SC
authors.lastname: Stevens
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhelms-University, University Medical Center, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.affiliation: Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Dane J
authors.initials: DJ
authors.lastname: Youtz
authors.affiliation: College of Nursing, The Ohio State University, Columbus, OH, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Clark
authors.affiliation: College of Nursing, The Ohio State University, Columbus, OH, USA.
authors.forename: Runfeng
authors.initials: R
authors.lastname: Jing
authors.affiliation: Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Reiser
authors.affiliation: Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Bicer
authors.affiliation: Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Devine
authors.affiliation: College of Nursing, The Ohio State University, Columbus, OH, USA; College of Nursing, Marquette University, Milwaukee, WI, USA.
authors.forename: Donna O
authors.initials: DO
authors.lastname: McCarthy
authors.affiliation: 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.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000473:pathology; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D020013:Calcium Signaling; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000150:complications* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D047368:Tumor Burden; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002316:Cardiotonic Agents; D016207:Cytokines; D000804:Angiotensin II; D005978:Glutathione; D019808:Losartan
keywords: Calcium signaling; Cancer cachexia; Cardiomyocyte; Cardiovascular function; Losartan