Role of Heme Oxygenase-1 in Human Endothelial Cells

  • Hevidar Taha
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Klaudia Skrzypek
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Ibeth Guevara
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Anneliese Nigisch
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Stefan Mustafa
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Anna Grochot-Przeczek
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Pawel Ferdek
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Halina Was
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Jerzy Kotlinowski
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Magdalena Kozakowska
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Aneta Balcerczyk
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Lucie Muchova
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Libor Vitek
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Guenter Weigel
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Jozef Dulak
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).
  • Alicja Jozkowicz
    From the Department of Thoracic Surgery (A.N., G.W.) and Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.M.), University of Vienna, Austria; Department of Molecular Biophysics, University of Lodz, Poland (A.B.); Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Czech Republic (L.M., L.V.).

書誌事項

タイトル別名
  • Lesson From the Promoter Allelic Variants
公開日
2010-08
DOI
  • 10.1161/atvbaha.110.207316
公開者
Ovid Technologies (Wolters Kluwer Health)

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説明

<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> Heme oxygenase-1 (HO-1) is an antioxidative, antiinflammatory, and cytoprotective enzyme that is induced in response to cellular stress. The HO-1 promoter contains a (GT)n microsatellite DNA, and the number of GT repeats can influence the occurrence of cardiovascular diseases. We elucidated the effect of this polymorphism on endothelial cells isolated from newborns of different genotypes. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> On the basis of HO-1 expression, we classified the HO-1 promoter alleles into 3 groups: short (S) (most active, GT ≤23), medium (moderately active, GT=24 to 28), and long (least active, GT ≥29). The presence of the S allele led to higher basal HO-1 expression and stronger induction in response to cobalt protoporphyrin, prostaglandin-J <jats:sub>2</jats:sub> , hydrogen peroxide, and lipopolysaccharide. Cells carrying the S allele survived better under oxidative stress, a fact associated with the lower concentration of oxidized glutathione and more favorable oxidative status, as determined by measurement of the ratio of glutathione to oxidized glutathione. Moreover, they proliferated more efficiently in response to vascular endothelial growth factor A, although the vascular endothelial growth factor–induced migration and sprouting of capillaries were not influenced. Finally, the presence of the S allele was associated with lower production of some proinflammatory mediators, such as interleukin-1β, interleukin-6, and soluble intercellular adhesion molecule-1. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusion—</jats:italic> </jats:bold> The (GT)n promoter polymorphism significantly modulates a cytoprotective, proangiogenic, and antiinflammatory function of HO-1 in human endothelium. </jats:p>

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