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Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes
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SYSNO ASEP 0395068 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes Author(s) Bohuslavová, Romana (BTO-N) RID
Škvorová, Lada (BTO-N)
Sedmera, David (FGU-C) RID, ORCID, SAI
Semenza, G.L. (US)
Pavlínková, Gabriela (BTO-N) RID, ORCIDSource Title Journal of Molecular and Cellular Cardiology. - : Elsevier - ISSN 0022-2828
Roč. 60, Jul (2013), s. 129-141Number of pages 13 s. Language eng - English Country GB - United Kingdom Keywords Diabetic embryopathy ; Heart defect ; Hypoxia-inducible factor 1 alpha Subject RIV EB - Genetics ; Molecular Biology Subject RIV - cooperation Institute of Physiology - Cardiovascular Diseases incl. Cardiotharic Surgery R&D Projects GA301/09/0117 GA ČR - Czech Science Foundation (CSF) GAP302/11/1308 GA ČR - Czech Science Foundation (CSF) Institutional support FGU-C - RVO:67985823 CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000320429100017 EID SCOPUS 84877675746 DOI 10.1016/j.yjmcc.2013.04.015 Annotation Cardiovascular malformations are the most common manifestation of diabetic embryopathy. The molecular mechanisms underlying the teratogenic effect of maternal diabetes have not been fully elucidated. Using genome-wide expression profiling, we previously demonstrated that exposure to maternal diabetes resulted in dysregulation of the hypoxia-inducible factor 1 (HIF-1) pathway in the developing embryo. We thus considered a possible link between HIF-1-regulated pathways and the development of congenital malformations. HIF-1 alpha heterozygous-null (Hif1a(+/-)) and wild type (Wt) littermate embryos were exposed to the intrauterine environment of a diabetic mother to analyze the frequency and morphology of congenital defects, and assess gene expression changes in Wt and Hif1a(+/-) embryos. We observed a decreased number of embryos per litter and an increased incidence of heart malformations, including atrioventricular septal defects and reduced myocardial mass, in diabetes-exposed Hif1a(+/-) embryos as compared to Wt embryos. We also detected significant differences in the expression of key cardiac transcription factors, including Nkx2.5, Tbx5, and Mef2C, in diabetes-exposed Hif1a(+/-) embryonic hearts compared to Wt littermates. Thus, partial global HIF-1 alpha deficiency alters gene expression in the developing heart and increases susceptibility to congenital defects in a mouse model of diabetic pregnancy. (C) 2013 Elsevier Ltd. All rights reserved. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2014
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