Adenoviral-mediated overexpression of catalase inhibits endothelial cell proliferation

Michela Zanetti, Zvonimir S Katusic, Timothy O'Brien

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although hydrogen peroxide (H2O2) induces proliferation of vascular smooth muscle cells, its role in endothelial cell proliferation is unclear. Our aim was to study the role of hydrogen peroxide in endothelial cell proliferation by overexpressing catalase. Human aortic endothelial cells were transduced with adenoviral vectors encoding β-galactosidase (Adβgal) or catalase (AdCat) or were exposed to diluent alone (control). Transgene expression was demonstrated by β-galactosidase staining, Western analysis, and significantly increased enzyme activity in AdCat-transduced cells. Overexpression of catalase decreased DNA synthesis in AdCat compared with control and Adβgal-transduced cells (536.8 ± 31 vs. 1,875.1 ± 132.9 vs. 1,347.5 ± 93.7 dpm/well, respectively; P < 0.05 vs. control and Adβgal). Six days after transduction with AdCat (multiplicity of infection = 50), cell numbers were significantly reduced (AdCat: 38 ± 1.8% of cell counts in control, P < 0.05; and 45 ± 2% of cell count in Adβgal, P < 0.05). Incubation with aminotriazole 10 mmol/l, an inhibitor of catalase, prevented this effect. The number of apoptotic cells was increased one- and threefold 2 and 4 days, respectively, after transduction with AdCat. Exogenous administration of low concentrations of H2O2 (50 μM) significantly increased cell proliferation, whereas it was inhibited by higher concentrations. These results suggest that H2O2 is an important modulator of endothelial cell proliferation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
StatePublished - Dec 1 2002

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Catalase
Endothelial Cells
Cell Proliferation
Cell Count
Galactosidases
Hydrogen Peroxide
Amitrole
Transgenes
Vascular Smooth Muscle
Smooth Muscle Myocytes
Staining and Labeling
DNA
Enzymes
Infection

Keywords

  • Apoptosis
  • Hydrogen peroxide

ASJC Scopus subject areas

  • Physiology

Cite this

Adenoviral-mediated overexpression of catalase inhibits endothelial cell proliferation. / Zanetti, Michela; Katusic, Zvonimir S; O'Brien, Timothy.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 6 52-6, 01.12.2002.

Research output: Contribution to journalArticle

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