title: Gene deletion of the kinin receptor B1 attenuates cardiac inflammation and fibrosis during the development of experimental diabetic cardiomyopathy.
abstract: OBJECTIVE
  Diabetic cardiomyopathy is associated with increased mortality in patients with diabetes. The underlying pathology of this disease is still under discussion. We studied the role of the kinin B1 receptor on the development of experimental diabetic cardiomyopathy.
  
  
  METHODS
  We utilized B1 receptor knockout mice and investigated cardiac inflammation, fibrosis, and oxidative stress after induction of streptozotocin (STZ)-induced diabetes. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes.
  
  
  RESULTS
  B1 receptor knockout mice showed an attenuation of diabetic cardiomyopathy with improved systolic and diastolic function in comparison with diabetic control mice. This was associated with a decreased activation state of the mitogen-activated protein kinase p38, less oxidative stress, as well as normalized cardiac inflammation, shown by fewer invading cells and no increase in matrix metalloproteinase-9 as well as the chemokine CXCL-5. Furthermore, the profibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor.
  
  
  CONCLUSIONS
  These findings suggest that the B1 receptor is detrimental in diabetic cardiomyopathy in that it mediates inflammatory and fibrotic processes. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human diabetic cardiomyopathy.
authors.affiliation: Department of Cardiology and Pneumology, Charité -Universitä tsmedizinBerlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Savvatis
authors.forename: Felcicitas
authors.initials: F
authors.lastname: Escher
authors.forename: Meike
authors.initials: M
authors.lastname: Sobirey
authors.forename: Alexander
authors.initials: A
authors.lastname: Riad
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
mesh_terms: D000818:Animals; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000503:physiopathology* / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology* / Q000517:prevention & control; D017353:Gene Deletion; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D043783:Receptor, Bradykinin B1 / Q000172:deficiency*; D016277:Ventricular Function, Left / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D043783:Receptor, Bradykinin B1; D048051:p38 Mitogen-Activated Protein Kinases