Redox signaling in an in vivo murine model of low magnitude oscillatory wall shear stress.
Wall Shear Stress (WSS) has been identified as an important factor in the pathogenesis of atherosclerosis. We utilized a novel murine aortic coarctation model to acutely create a region of low magnitude oscillatory WSS in vivo. We employed this model to test the hypothesis that acute changes in WSS in vivo induce upregulation of inflammatory proteins, mediated by reactive oxygen species (ROS). Superoxide generation and VCAM-1 expression both increased in regions of low magnitude oscillatory WSS. WSS-dependent superoxide formation was attenuated by tempol treatment, but was unchanged in p47 phox knockout (ko) mice. However, in both the p47 phox ko mice and the tempol-treated mice, low magnitude oscillatory WSS produced an increase in VCAM-1 expression comparable to control mice. Additionally, this same VCAM-1 expression was observed in ebselen-treated mice and catalase overexpressing mice. These results suggest that although the redox state is important to the overall pathogenesis of atherosclerosis, the initial WSS-dependent inflammatory response leading to lesion localization is not dependent on ROS.
Willett
Nick J
NJ
The Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Kundu
Kousik
K
Knight
Sarah F
SF
Dikalov
Sergey
S
Murthy
Niren
N
Taylor
W Robert
WR
D000818:Animals; D001017:Aortic Coarctation / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D033081:Shear Strength; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D013481:Superoxides / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases