title: Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice.
abstract: BACKGROUND
  Pulmonary hypertension and subsequent right ventricular (RV) failure are associated with high morbidity and mortality. Prognosis is determined by occurrence of RV failure. Currently, adequate treatment for RV failure is lacking. Further research into the molecular basis for the development of RV failure as well as the development of better murine models of RV failure are therefore imperative. We hypothesize that adding a low-copper diet to chronic hypoxia in mice reinforces their individual effect and that the combination of mild pulmonary vascular remodeling and capillary rarefaction, induces RV failure.
  
  
  METHODS
  Six week old mice were subjected to normoxia (N; 21% O2) or hypoxia (H; 10% O2) during a period of 8 weeks and received either a normal diet (Cu+) or a copper depleted diet (Cu-). Cardiac function was assessed by echocardiography and MRI analysis.
  
  
  CONCLUSIONS
  Here, we characterized a mouse model of chronic hypoxia combined with a copper depleted diet and demonstrate that eight weeks of chronic hypoxia (10%) is sufficient to induce RV hypertrophy and subsequent RV failure. Addition of a low copper diet to hypoxia did not have any further deleterious effects on right ventricular remodeling.
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ella M
authors.initials: EM
authors.lastname: Poels
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bitsch
authors.affiliation: Department of Radiology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Jos M
authors.initials: JM
authors.lastname: Slenter
authors.affiliation: Department of Radiology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: M Eline
authors.initials: ME
authors.lastname: Kooi
authors.affiliation: Department of Respiratory Medicine, NUTRIM School Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Chiel C
authors.initials: CC
authors.lastname: de Theije
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: de Windt
authors.affiliation: Department of Cardiology, Heart Vessel Center, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Vanessa P M
authors.initials: VP
authors.lastname: van Empel
authors.affiliation: Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Paula A
authors.initials: PA
authors.lastname: da Costa Martins
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology*; D006976:Hypertension, Pulmonary / Q000150:complications; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia; D008297:Male; D051379:Mice; D013312:Stress, Physiological; D013318:Stroke Volume; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D003300:Copper
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