| Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus. | |
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MedLine Citation:
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PMID: 16937126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy. MATERIALS AND METHODS: Diabetes mellitus was induced by streptozotocin (50 mg/kg i.p. for 5 days) in 20 C57/BL6J mice. Diabetic mice were treated daily with the p38 MAPK inhibitor SB 203580 (1 mg/kg daily, n=10) or with placebo (n=10) and were compared to non-diabetic controls. Left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes mellitus. The parameters for systolic function were the end systolic pressure-volume relationship (ESPVR) and the left ventricular end systolic pressure. The parameters for diastolic function were the left ventricular end diastolic pressure and the end diastolic pressure-volume relationship (EDPVR). Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-alpha, IL6, IL1-beta, and TGF-beta1. Phosphorylation of MAPK p38 was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining. RESULTS: Left ventricular dysfunction was documented by impaired ESPVR and EDPVR. Cardiac cytokine levels and cardiac fibrosis were increased in diabetic animals compared to controls. Treatment with the p38 inhibitor normalised cardiac cytokine levels and improved systolic function, but did not change cardiac fibrosis and diastolic dysfunction compared to placebo. CONCLUSIONS/INTERPRETATION: Pharmacological inhibition of p38 MAPK prevents cardiac inflammation and attenuates left ventricular dysfunction in diabetic cardiomyopathy. |
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Authors:
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D Westermann; S Rutschow; S Van Linthout; A Linderer; C Bücker-Gärtner; M Sobirey; A Riad; M Pauschinger; H-P Schultheiss; C Tschöpe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-26 |
Journal Detail:
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Title: Diabetologia Volume: 49 ISSN: 0012-186X ISO Abbreviation: Diabetologia Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-06 Completed Date: 2007-03-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 2507-13 Citation Subset: IM |
Affiliation:
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Department of Cardiology and Pneumology, Charité University Hospital, Benjamin Franklin Campus, Berlin, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Weight Cytokines / metabolism* Diabetes Mellitus, Experimental / enzymology, physiopathology* Diabetic Angiopathies / physiopathology, prevention & control Enzyme Inhibitors / therapeutic use Heart / anatomy & histology, physiopathology* Imidazoles / therapeutic use Inflammation / physiopathology Male Mice Mice, Inbred C57BL Organ Size Phosphorylation Pyridines / therapeutic use Systole / physiology Ventricular Dysfunction, Left / physiopathology*, prevention & control Ventricular Function, Left p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Pyridines; 0/SB 203580; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
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