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Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice
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SYSNO ASEP 0433865 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice Author(s) Bohuslavová, Romana (BTO-N) RID
Kolář, František (FGU-C) RID, ORCID, SAI
Sedmera, David (FGU-C) RID, ORCID, SAI
Škvorová, Lada (BTO-N)
Papoušek, František (FGU-C)
Neckář, Jan (FGU-C) RID, ORCID
Pavlínková, Gabriela (BTO-N) RID, ORCIDSource Title BMC Endocrine Disorders. - : BioMed Central Ltd.
Roč. 14, Feb 6 (2014)Number of pages 14 s. Language eng - English Country GB - United Kingdom Keywords Echocardiographic parameters ; Hypoxia inducible factor 1 alpha ; Diabetic cardiomyopathy Subject RIV FB - Endocrinology, Diabetology, Metabolism, Nutrition R&D Projects GA301/09/0117 GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support FZU-D - RVO:68378271 CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000334624800001 DOI 10.1186/1472-6823-14-11 Annotation Background:Diabetic cardiomyopathy is associated with a number of functional and structural pathological changes such as left ventricular dysfunction, cardiac remodeling, and apoptosis.The primary cause of diabetic cardiomyopathy is hyperglycemia, the metabolic hallmark of diabetes.Recent studies have shown that a diabetic environment suppresses hypoxia-inducible factor (HIF)-1 alpha protein stability and function.The aim of this study was to analyze the functional role of HIF-1 alpha in the development of diabetic cardiomyopathy.We have hypothesized that the partial deficiency of HIF-1 alpha may compromise cardiac responses under diabetic conditions and increase susceptibility to diabetic cardiomyopathy.Methods:Diabetes was induced by streptozotocin in wild type (Wt) and heterozygous Hif1a knock-out (Hif1a(+/-))mice.Echocardiographic evaluations of left ventricular functional parameters,expression analyses by qPCR and Western blot,and cardiac histopathology assessments were performed in age-matched groups,diabetic,and non-diabetic Wt and Hif1a(+/-)mice.Results: Five weeks after diabetes was established,a significant decrease in left ventricle fractional shortening was detected in diabetic Hif1a(+/-)but not in diabetic Wt mice.The combination effects of the partial deficiency of Hif1a and diabetes affected the gene expression profile of the heart,including reduced vascular endothelial growth factor A (Vegfa) expression.Adverse cardiac remodeling in the diabetic Hif1a(+/-)heart was shown by molecular changes in the expression of structural molecules and components of the extracellular matrix.Conclusions:We have shown a correlation between heterozygosity for Hif1a and adverse functional,molecular,and cellular changes associated with diabetic cardiomyopathy. Our results provide evidence that HIF-1 alpha regulates early cardiac responses to diabetes, and that HIF-1 alpha deregulation may influence the increased risk for diabetic cardiomyopathy. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2015
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