| Bosentan attenuates cardiac fibrosis in diabetic mice without affecting blood glucose. | |
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MedLine Citation:
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PMID: 21844133 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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INTRODUCTION: : cardiac complication in diabetic patients remained high despite very good control of blood glucose. Our hypothesis is that it was associated with a persistently high endothelin-1 (ET-1) level. To clarify this notion we created a diabetic model by streptozotocin (STZ) injection. Since dysfunction of endothelial cells, which are the main source of ET-1, is believed to have an important role in the pathophysiology of diabetic complications, Bosentan (a non-selective endothelin receptor antagonist) was administered to block ET-1 activity. Aims: to investigate the potential protective effect of Bosentan in diabetic myocardial fibrosis. MATERIALS AND METHODS: : 6-week-old male C57BL/6 mice with were divided into three groups (N = 20): control group, DM group (diabetes group) and DM-B group (diabetes with bosentan group). STZ was injected with 200 mg/g, single dose, i.p. (intraperitoneal injection) to make a type 1 diabetic model. Fasting blood glucose (FBG) was measured at weeks 0, 1, and 2 after STZ injection to confirm that the diabetic model existed. Bosentan (100 mg/kg) and placebo were given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. Cardiac fibrosis was evaluated by morphometric analysis. The differences of mRNA expression were compared by real-time PCR. Cardiac systolic function was evaluated by echocardiography. RESULTS: : after 18 weeks of diabetic situation, the FBG of DM-B mice was significantly higher than that of control mice and was similar to that of DM mice (DM mice vs. control mice, p < 0.001; DM-B vs. control mice, p < 0.001; DM mice vs. DM-B mice, p > 0.05). Pathological analysis with Masson's Trichrome staining showed significant fibrotic changes in diabetic myocardium, and the fibrosis was ameliorated by bosentan. Furthermore, the area of interstitial fibrosis was markedly lower in DM-B mice. This lower area of interstitial fibrosis is associated with higher expression of cardiac VEGF mRNA (a potent angiogenic factor) in DM-B mice than in DM mice (p < 0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-ß, CTGF and collagen-1) than in DM mice (p < 0.01). Furthermore, cardiac systolic function (fractional shortening, FS) of DM and DM-B mice decreased after 18 weeks of diabetes (DM vs. control mice, p < 0.001). However, the impairment of cardiac function (FS) was significantly ameliorated, even nearly normalized, by bosentan (DM-B vs. control mice, p > 0.05). CONCLUSIONS: these findings indicate the potential usefulness of a ET receptor antagonist bosentan in the amelioration of diabetic cardiac complications (myocardial fibrosis and cardiac dysfunction) without affecting blood glucose. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis. |
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Authors:
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Bo Yang; Yun-Dai Chen; Min Li; Fei-Hu Zhou; Yong Xu; Guang-Yi Wang; Tian-De Li; You-Hong Xing |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-15 |
Journal Detail:
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Title: Journal of the renin-angiotensin-aldosterone system : JRAAS Volume: - ISSN: 1752-8976 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100971636 Medline TA: J Renin Angiotensin Aldosterone Syst Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Cardiology, Chinese PLA General Hospital, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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