| Cardiac-specific overexpression of HIF-1{alpha} prevents deterioration of glycolytic pathway and cardiac remodeling in streptozotocin-induced diabetic mice. | |
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MedLine Citation:
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PMID: 20566749 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Defective glycolysis and angiogenesis in the heart of diabetic patients and in experimental diabetic animal models have been reported. The aim of this study was to determine whether overexpression of hypoxia-inducible factor (HIF)-1alpha protects from myocardial injury in diabetic mice by increasing myocardial glycolysis and angiogenesis. Cardiac-specific HIF-1alpha-overexpressing transgenic and age-matched wild-type control mice were treated with streptozotocin to induce diabetes. Changes in glucose transporters, glycolytic enzymes, angiogenic factors and cardiac morphology were examined in the hearts by real-time RT-PCR, Western blotting, enzymatic assay, and histological assays. HIF-1alpha overexpression elevated hexokinase II (HK-II) protein level and total HK activity in nondiabetic heart and prevented the decreases in HK-II mRNA, protein, and total HK activity in diabetic heart. In addition, the reduction of glucose transporter I, but not glucose transporter 4, was restored in HIF transgenic mouse heart along with a recovery of myocardium ATP production. HIF-1alpha overexpression also normalized diabetes-reduced vascular endothelial growth factor concentration along with a sustained myocardial capillary density and an inhibition of cardiomyocyte hypertrophy and cardiac fibrosis. Therefore, elevation of HIF-1alpha provides a cardiac protection from diabetic-induced impairment in glucose metabolism and angiogenesis via up-regulation of HIF-1 target genes. |
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Authors:
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Wanli Xue; Lu Cai; Yi Tan; Patricia Thistlethwaite; Y James Kang; Xiaokun Li; Wenke Feng |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-21 |
Journal Detail:
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Title: The American journal of pathology Volume: 177 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-07 Completed Date: 2010-12-06 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 97-105 Citation Subset: AIM; IM |
Affiliation:
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Departments of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Cell Line Diabetes Mellitus, Experimental* / metabolism, pathology Glucose / metabolism Glucose Transporter Type 1 / genetics, metabolism Glycolysis / physiology* Hexokinase / metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics, metabolism* Mice Mice, Transgenic Myocardium / cytology, metabolism*, pathology Myocytes, Cardiac / cytology, metabolism Ventricular Remodeling / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL63760/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 1; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 2.7.1.1/Hexokinase |
| Comments/Corrections | |
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