Angiogenic Gene Expression in Down Syndrome Fetal Hearts

2015 ◽  
Vol 40 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Olga Sánchez ◽  
Carmen Domínguez ◽  
Aina Ruiz ◽  
Irene Ribera ◽  
Jaume Alijotas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Growth Factor ◽  
Heart Defects ◽  
Hypoxia Inducible Factor ◽  
Transcript Level ◽  
Heart Tissue ◽  
Angiogenic Factors ◽  
Heme Oxygenase 1 ◽  
Endothelial Growth Factor

Introduction: Forty percent of Down syndrome (DS) fetuses have congenital heart defects (CHD). An abnormal angiogenic environment has been described in euploid fetuses with CHD. However, the underlying pathophysiologic pathway that contributes to CHD in DS remains unknown. The objective was to compare the expression of angiogenic factors and chronic hypoxia genes in heart tissue from DS and euploid fetuses with and without CHD. Methods: The gene expression profile was determined by real-time PCR quantification in heart tissue from 33 fetuses with DS, 23 euploid fetuses with CHD and 23 control fetuses. Results: Angiogenic factors mRNA expression was significantly increased in the DS group compared to the controls (soluble fms-like tyrosine kinase-1, 81%, p = 0.007; vascular endothelial growth factor A, 57%, p = 0.006, and placental growth factor, 32%, p = 0.0227). Significant increases in the transcript level of hypoxia-inducible factor-2α and heme oxygenase 1 were also observed in the DS group compared to the controls. The expression of angiogenic factors was similar in DS fetuses and CHD euploid fetuses with CHD. Conclusion: Abnormal angiogenesis was detected in the hearts of DS fetuses with and without CHD. Our results suggest that DS determines an intrinsically angiogenic impairment that may be present in the fetal heart.

scholarly journals Induction of Hypoxia-inducible Factor 1α Gene Expression by Vascular Endothelial Growth Factor

2008 ◽  
Vol 283 (17) ◽  
pp. 11435-11444 ◽  
Author(s):  
Juan José P. Deudero ◽  
Carlos Caramelo ◽  
María Carmen Castellanos ◽  
Fernando Neria ◽  
Ruth Fernández-Sánchez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Hypoxia Inducible Factor 1Α ◽  
Endothelial Growth Factor

scholarly journals Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.

1996 ◽  
Vol 16 (9) ◽  
pp. 4604-4613 ◽  
Author(s):  
J A Forsythe ◽  
B H Jiang ◽  
N V Iyer ◽  
F Agani ◽  
S W Leung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Reporter Gene ◽  
Hypoxia Inducible Factor ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Vascular Endothelial ◽  
Hypoxia Inducible Factor 1 ◽  
Endothelial Growth Factor

Expression of vascular endothelial growth factor (VEGF) is induced in cells exposed to hypoxia or ischemia. Neovascularization stimulated by VEGF occurs in several important clinical contexts, including myocardial ischemia, retinal disease, and tumor growth. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein that activates transcription of the human erythropoietin gene in hypoxic cells. Here we demonstrate the involvement of HIF-1 in the activation of VEGF transcription. VEGF 5'-flanking sequences mediated transcriptional activation of reporter gene expression in hypoxic Hep3B cells. A 47-bp sequence located 985 to 939 bp 5' to the VEGF transcription initiation site mediated hypoxia-inducible reporter gene expression directed by a simian virus 40 promoter element that was otherwise minimally responsive to hypoxia. When reporters containing VEGF sequences, in the context of the native VEGF or heterologous simian virus 40 promoter, were cotransfected with expression vectors encoding HIF-1alpha and HIF-1beta (ARNT [aryl hydrocarbon receptor nuclear translocator]), reporter gene transcription was much greater in both hypoxic and nonhypoxic cells than in cells transfected with the reporter alone. A HIF-1 binding site was demonstrated in the 47-bp hypoxia response element, and a 3-bp substitution eliminated the ability of the element to bind HIF-1 and to activate transcription in response to hypoxia and/or recombinant HIF-1. Cotransfection of cells with an expression vector encoding a dominant negative form of HIF-1alpha inhibited the activation of reporter transcription in hypoxic cells in a dose-dependent manner. VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells.

BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1α, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3767-3775 ◽  
Author(s):  
Matthias Mayerhofer ◽  
Peter Valent ◽  
Wolfgang R. Sperr ◽  
James D. Griffin ◽  
Christian Sillaber
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Vegf Mrna ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

Recent data suggest that vascular endothelial growth factor (VEGF), a cytokine involved in autocrine growth of tumor cells and tumor angiogenesis, is up-regulated and plays a potential role in myelogenous leukemias. In chronic myelogenous leukemia (CML), VEGF is expressed at high levels in the bone marrow and peripheral blood. We show here that the CML-associated oncogene BCR/ABL induces VEGF gene expression in growth factor–dependent Ba/F3 cells. Whereas starved cells were found to contain only baseline levels of VEGF mRNA, Ba/F3 cells induced to express BCR/ABL exhibited substantial amounts of VEGF mRNA. BCR/ABL also induced VEGF promoter activity and increased VEGF protein levels in Ba/F3 cells. Moreover, BCR/ABL was found to promote the expression of functionally active hypoxia-inducible factor-1 (HIF-1), a major transcriptional regulator of VEGF gene expression. BCR/ABL-induced VEGF gene expression was counteracted by the phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the mitogen-activated protein kinase pathway. Similarly, BCR/ABL-dependent HIF-1α expression was inhibited by the addition of LY294002 and rapamycin. Together, our data show that BCR/ABL induces VEGF- and HIF-1α gene expression through a pathway involving PI3-kinase and mTOR. BCR/ABL-induced VEGF expression may contribute to the pathogenesis and increased angiogenesis in CML.

scholarly journals Downregulation of flt-1 and HIF-1α Gene Expression by Some Antioxidants in Rats Under Sodium Nitrite–Induced Hypoxic Stress

Dose-Response ◽  
2018 ◽  
Vol 16 (2) ◽  
pp. 155932581877620
Author(s):  
Laila Mohamed Fadda ◽  
Hala A. Attia ◽  
Nouf Mohamed Al-Rasheed ◽  
Hanaa Mahmoud Ali ◽  
Nawal Mohamed Al-Rasheed
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Sodium Nitrite ◽  
Histopathological Examination ◽  
Hypoxia Inducible Factor ◽  
Elevated Serum ◽  
Combination Regimen ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

This study assessed the effect of L-arginine (L-argin), carnosine (carno), or their combination in the amelioration of certain biochemical indices induced in the liver of hypoxic rats. Hypoxia was induced via sodium nitrite (S.nit) injection at a dose of 75 mg/kg. Rats were administered L-argin (250 mg/kg) or carno (250 mg/kg), either alone or in combination, 24 hours and 1 hour prior to S.nit intoxication. Hypoxia significantly elevated serum alanine aminotransferase, in addition to a significant upregulation of hepatic heat shock protein 70 with concurrent reduction in the level of vascular endothelial growth factor. Moreover, hepatic vascular endothelial growth factor 1 (flt-1), hypoxia inducible factor-1α gene expression, and cytochrome P450 levels were elevated, compared with the normoxic group. The antioxidants, administered either alone or in combination, markedly downregulated all of the previously mentioned biomarkers, compared to the hypoxic rats. Histopathological examination revealed hepatocellular degeneration and nuclear pyknosis, in addition to inflammatory cellular infiltration in the hypoxic rats, whereas treatment with the studied antioxidants improved the liver architecture. The present data revealed the efficacy of L-argin and carno in ameliorating the hepatic damage induced via angiogenic markers in response to hypoxia, the combination regimen showing the superior effect.

scholarly journals Expression of Hypoxia-Inducible Factor (HIF)-1αand Vascular Endothelial Growth Factor (VEGF)-D As Outcome Predictors in Resected Esophageal Squamous Cell Carcinoma

2008 ◽  
Vol 25 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Ching Tzao ◽  
Shih-Chun Lee ◽  
Ho-Jui Tung ◽  
Han-Shui Hsu ◽  
Wen-Hu Hsu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Hypoxia Inducible Factor ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Angiogenic Factors ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Hypoxia-inducible factor (HIF)-1αand vascular endothelial growth factor (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C, prognostic significance of VEGF-D expression and its association with HIF-1αexpression remain elusive in esophageal squamous cell cancer (ESCC). We studied expression of HIF-1αand VEGF-D using immunohistochemistry in 85 resected ESCC specimens and correlated results with patients' clinicopathologic parameters and survival. Association between expression of HIF-1αand VEGF-D was investigated using a concordance analysis. High expression of HIF-1αand VEGF-D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1αexpression correlated well with tumor stage (P= 0.041), whereas VEGF-D expression correlated with tumor stage (P= 0.027) and N status (P= 0.019). Groups of high HIF-1αand VEGF-D showed worse survivals than those of low expression (P= 0.002 and 0.001, respectively). Multivariate analysis supported expression of HIF-1αand VEGF-D as significant survival predictors (P= 0.044 and 0.035, respectively). A concordance rate of 69.5% was observed between expression of HIF-1αand VEGF-D. In conclusion, protein expression of HIF-1αand VEGF-D are independent prognostic predictors. An association between expression of HIF-1αand VEGF-D suggests that these two angiogenic factors are essential in progression of ESCC.

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