About: Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice     Goto   Sponge   NotDistinct   Permalink

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  • 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.
  • 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. (en)
Title
  • Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice
  • Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice (en)
skos:prefLabel
  • Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice
  • Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice (en)
skos:notation
  • RIV/00216208:11110/14:10272171!RIV15-MSM-11110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED1.1.00/02.0109), P(GA301/09/0117), Z(AV0Z50520701)
http://linked.open...iv/cisloPeriodika
  • February
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 35799
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11110/14:10272171
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • Heterozygous Hif1a knock-out; Vascular endothelial growth factor A; Diabetic cardiomyopathy; Hypoxia inducible factor 1 alpha; Echocardiographic parameters (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [E6EC74929C8F]
http://linked.open...i/riv/nazevZdroje
  • BMC Endocrine Disorders
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 14
http://linked.open...iv/tvurceVysledku
  • Neckář, Jan
  • Kolář, František
  • Sedmera, David
  • Papoušek, František
  • Bohuslavová, Romana
  • Pavlínková, Gabriela
  • Škvorová, Lada
http://linked.open...ain/vavai/riv/wos
  • 000334624800001
http://linked.open...n/vavai/riv/zamer
issn
  • 1472-6823
number of pages
http://bibframe.org/vocab/doi
  • 10.1186/1472-6823-14-11
http://localhost/t...ganizacniJednotka
  • 11110
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