Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

Anna Csiszar, Nazar Labinskyy, Viviana Perez, Fabio A. Recchia, Andrej Podlutsky, Partha Mukhopadhyay, Gyorgy Losonczy, Pal Pacher, Steven N. Austad, Andrzej Bartke, Zoltan Ungvari

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•- and H2O 2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•- and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•- and H 2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.

Original languageEnglish (US)
Pages (from-to)H1882-H1894
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 2008

Keywords

  • Atherosclerosis
  • Prop1 mice
  • Senescence
  • Vascular disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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