Gene Deletion of the Kinin Receptor B1 Attenuates Cardiac Inflammation and Fibrosis During the Development of Experimental Diabetic Cardiomyopathy

  1. Dirk Westermann1,
  2. Thomas Walther1,
  3. Konstantinos Savvatis1,
  4. Felcicitas Escher1,
  5. Meike Sobirey1,
  6. Alexander Riad1,
  7. Michael Bader2,
  8. Heinz-Peter Schultheiss1 and
  9. Carsten Tschöpe1
  1. 1Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;
  2. 2Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
  1. Corresponding author: Carsten Tschöpe, carsten.tschoepe{at}


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.

RESEARCH DESIGN AND 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.


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    • Received March 7, 2008.
    • Accepted March 2, 2009.
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  1. Diabetes vol. 58 no. 6 1373-1381
  1. All Versions of this Article:
    1. db08-0329v1
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