"JUL" . "11110" . . . . . . . "79493" . . "Journal of Molecular and Cellular Cardiology" . "1"^^ . . . "Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes"@en . . "Hypoxia-inducible factor 1 alpha; Heart defect; Diabetic embryopathy"@en . "[325661172262]" . . "Bohuslavov\u00E1, Romana" . . . "13"^^ . "5"^^ . "Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes" . . . "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."@en . "60" . . "000320429100017" . . . "Sedmera, David" . "http://dx.doi.org/10.1016/j.yjmcc.2013.04.015" . "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." . "0022-2828" . . "Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes"@en . "RIV/00216208:11110/13:10188753!RIV14-MSM-11110___" . . . "I, P(GA301/09/0117), P(GAP302/11/1308), V, Z(AV0Z50520701)" . "RIV/00216208:11110/13:10188753" . "\u0160kvorov\u00E1, Lada" . "Pavl\u00EDnkov\u00E1, Gabriela" . "10.1016/j.yjmcc.2013.04.015" . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "Semenza, Gregg L." . "Increased susceptibility of HIF-1 alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes" .