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

Westermann D, Walther T, Savvatis K, Escher F, Sobirey M, Riad A, Bader M, Schultheiss HP, Tschöpe C - Diabetes (2009)

Bottom Line: The underlying pathology of this disease is still under discussion.Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Pneumology, Charité -Universitä tsmedizinBerlin, Campus Benjamin Franklin, Berlin, Germany.

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.

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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Related in: MedlinePlus

Increased levels of CTGF (A) and collagen type 1 (B) and 3 (C) in cardiac tissue of B1R+/+-STZ compared with nondiabetic controls. B1R−/−-STZ have normalized cardiac fibrosis as well as normalized levels of CTGF. *P < 0.05 vs. B1R+/+- and B1R−/−-STZ.
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Figure 7: Increased levels of CTGF (A) and collagen type 1 (B) and 3 (C) in cardiac tissue of B1R+/+-STZ compared with nondiabetic controls. B1R−/−-STZ have normalized cardiac fibrosis as well as normalized levels of CTGF. *P < 0.05 vs. B1R+/+- and B1R−/−-STZ.

Mentions: CTGF was highly increased in diabetic animals. This increase in CTGF was accompanied by increased levels of collagen type 1 and 3, as an indicator of cardiac fibrosis. In contrast, CTGF was normalized in B1R−/−-STZ, which translated into normalized collagen type 1 and type 3 levels as well, when compared with the controls (Fig. 7).


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

Westermann D, Walther T, Savvatis K, Escher F, Sobirey M, Riad A, Bader M, Schultheiss HP, Tschöpe C - Diabetes (2009)

Increased levels of CTGF (A) and collagen type 1 (B) and 3 (C) in cardiac tissue of B1R+/+-STZ compared with nondiabetic controls. B1R−/−-STZ have normalized cardiac fibrosis as well as normalized levels of CTGF. *P < 0.05 vs. B1R+/+- and B1R−/−-STZ.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682670&req=5

Figure 7: Increased levels of CTGF (A) and collagen type 1 (B) and 3 (C) in cardiac tissue of B1R+/+-STZ compared with nondiabetic controls. B1R−/−-STZ have normalized cardiac fibrosis as well as normalized levels of CTGF. *P < 0.05 vs. B1R+/+- and B1R−/−-STZ.
Mentions: CTGF was highly increased in diabetic animals. This increase in CTGF was accompanied by increased levels of collagen type 1 and 3, as an indicator of cardiac fibrosis. In contrast, CTGF was normalized in B1R−/−-STZ, which translated into normalized collagen type 1 and type 3 levels as well, when compared with the controls (Fig. 7).

Bottom Line: The underlying pathology of this disease is still under discussion.Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Pneumology, Charité -Universitä tsmedizinBerlin, Campus Benjamin Franklin, Berlin, Germany.

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.

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.

Show MeSH
Related in: MedlinePlus