title: Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade.
abstract: BACKGROUND
  The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease.
  
  
  OBJECTIVE
  To compare the severity of experimental PH between male and female athymic rats.
  
  
  METHODS
  PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed.
  
  
  RESULTS
  Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males.
  
  
  CONCLUSIONS
  Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.
authors.affiliation: TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Julien
authors.initials: J
authors.lastname: Guihaire
authors.affiliation: TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Deuse
authors.affiliation: TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, University of Paris-Sud, 92350 Le Plessis-Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
authors.affiliation: TSI Laboratory, University Heart Center Hamburg, 20246 Hamburg, Germany ; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany ; Cardiovascular Surgery, University Heart Center Hamburg, 20246 Hamburg, Germany ; Department of Cardiothoracic Surgery and Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Schrepfer
mesh_terms: D000818:Animals; D017352:Echo-Planar Imaging; D005260:Female; D005455:Fluorescent Antibody Technique; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D040262:Receptors, Vascular Endothelial Growth Factor