Long-term cyclic strain downregulates endothelial Nox4.
Antioxid Redox Signal
; 11(10): 2385-97, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19309265
ABSTRACT
Endothelial cells in vivo are constantly exposed to mechanical forces such as cyclic strain. In endothelial cells, Nox4-containing NAD(P)H oxidase complexes have been identified as major sources of superoxide anion (.O(2)(-)) formation. In this study, we analyzed the effect of cyclic strain on endothelial ROS formation by electron paramagnetic resonance spectroscopy, cytochrome c assay, and dihydroethidium fluorescence, on NO formation by Griess reaction and on gene expression by RT-PCR and Western blot. Primary cultures of human umbilical vein endothelial cells were exposed to 2-18% cyclic strain for up to 24 h using the Flexercell system. Long-term application of 5-12% cyclic strain downregulated Nox4 expression and ROS formation in a time-dependent manner. Downregulation of Nox4 was further confirmed by promoter analysis using dual-luciferase assay. Cu/Zn SOD, MnSOD, and catalase expression was decreased after application of chronic 12% cyclic strain. In contrast, endothelial NO formation and eNOS were increased by cyclic strain. Strain-dependent Nox4 downregulation was abolished by eNOS inhibition with L-NAME. In conclusion, physiological levels of cyclic strain downregulate Nox4 expression and superoxide anion formation. This novel mechanism might contribute to a vasoprotective balance between NO and superoxide anions in response to physiological mechanical stimulation of endothelial cells.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Endotelio Vascular
/
NADPH Oxidasas
/
Células Endoteliales
Idioma:
En
Revista:
Antioxid Redox Signal
Asunto de la revista:
METABOLISMO
Año:
2009
Tipo del documento:
Article