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

作者：Westermann Dirk; Walther Thomas; Savvatis Konstantinos; Escher Felcicitas; Sobirey Meike; Riad Alexander; Bader Michael; Schultheiss Heinz Peter; Tschoepe Carsten

来源：Diabetes, 2009, 58(6): 1373-1381.

DOI：10.2337/db08-0329

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 mid fibrotic processes. These insights might have useful implications oil future studies utilizing B1 receptor antagonists; for treatment of human diabetic cardiomyopathy. Diabetes 58:1373-1381, 2009

• 出版日期2009-6