Anti-atherogenic effect of laminar shear stress via Nrf2 activation.

Abstract:

:Fluid shear stress plays a critical role in the regulation of vascular biology and its pathology, such as atherosclerosis, via modulation of redox balance. Both pro-atherogenic (either oscillatory or turbulent, nonunidirectional) shear stress and anti-atherogenic (either steady or pulsatile, unidirectional laminar) shear stress stimulate production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are involved in signal transduction of gene expression. Nonunidirectional shear stress induces pro-atherogenic genes encoding adhesion molecules and chemokines in a manner dependent on production of both superoxide and nitric oxide. Steady or pulsatile laminar shear stress induces expression of genes encoding cytoprotective enzymes for glutathione biosynthesis and detoxification, which are regulated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). We show that pulsatile laminar shear stress (PLSS)-induced expression of adhesion molecules and chemokines was enhanced in human umbilical vein endothelial cells (HUVEC) treated with Nrf2 siRNA and arterial endothelial cells isolated from Nrf2 knockout mice. Hence, we propose the hypothesis that PLSS maintains the endothelium in an anti-atherogenic state via intracellular antioxidant levels increased as a result of Nrf2 activation, thereby preventing excess ROS/RNS production required for pro-atherogenic gene expression.

journal_name

Antioxid Redox Signal

authors

Takabe W,Warabi E,Noguchi N

doi

10.1089/ars.2010.3433

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

1415-26

issue

5

eissn

1523-0864

issn

1557-7716

journal_volume

15

pub_type

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