Gene deletion of the kinin receptor B1 attenuates cardiac inflammation and fibrosis during the development of experimental diabetic cardiomyopathy

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Item Type:	Article
Title:	Gene deletion of the kinin receptor B1 attenuates cardiac inflammation and fibrosis during the development of experimental diabetic cardiomyopathy
Creators Name:	Westermann, D., Walther, T., Savvatis, K., Sobirey, M., Riad, A., Bader, M., Schultheiss, H.P. and Tschoepe, C.
Abstract:	Objective: Diabetic cardiomyopathy is associated with increased mortality in patients with diabetes mellitus. 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 investiged cardiac inflammation, fibrosis and oxidative stress after induction of streptozotocin (STZ)-induced diabetes mellitus. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes mellitus. 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 MAP 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 pro-fibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor. Conclusion: 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.
Keywords:	Blood Pressure, Cardiomyopathies, Experimental Diabetes Mellitus, Diabetic Angiopathies, Gene Deletion, Heart Diseases, Inflammation, Oxidative Stress, Phosphorylation, Bradykinin B1 Receptor, Left Ventricular Function, p38 Mitogen-Activated Protein Kinases, Animals, Mice
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Volume:	58
Number:	6
Page Range:	1373-1381
Date:	June 2009
Official Publication:	https://doi.org/10.2337/db08-0329
PubMed:	View item in PubMed

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