title: Hemodynamic shear stress modulates endothelial cell autophagy: Role of LOX-1.
abstract: OBJECTIVE
  Shear stress, autophagy and LOX-1 are important players in atherogenesis. Direct impact of shear stress on autophagy development in endothelial cells and role of LOX-1 therein are undelineated.
  
  
  RESULTS
  A parallel-plate flow chamber was used to vary shear stress (3 to 30 dyn/cm(2)), and determine autophagy in endothelial cells. We observed that low shear stress (3 dyn/cm(2)) enhanced autophagy (expression of LC3-II) 2-3 fold, and increasing shear stress (15 to 30 dyn/cm(2)) resulted in a gradual decline. Autophagy increased when cells were treated with an inflammatory stimulus lipopolysaccharide (LPS). LOX-1 expression paralleled autophagy development. The in vitro observations were confirmed in the in vivo setting by studying autophagy (LC3-II and Beclin-1) and LOX-1 expression in wild-type mice given LPS. Expression of both autophagy and LOX-1 was most pronounced in aorto-iliac bifurcation region where shear stress is lower compared with aortic arch, thoracic aorta and iliac artery. To define the role of LOX-1 in the development of autophagy, we studied LOX-1 knockout mice. These mice despite LPS administration exhibited less autophagy (vs. wild-type mice). Role of LOX-1 in the regulation of autophagy was further established with LOX-1 inhibition (siRNA transfection and use of antibody) or overexpression (cDNA transfection), which showed that LOX-1 knockdown reduced while LOX-1 overexpression enhanced LC3-II expression in endothelial cells.
  
  
  CONCLUSIONS
  These observations suggest that low shear stress is a powerful regulator on autophagy, particularly in state of inflammation, and LOX-1 plays an important role in shear stress induced autophagy.
authors.affiliation: Central Arkansas Veterans Healthcare System, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China; School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, PR China.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Central Arkansas Veterans Healthcare System, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: SLiu2@uams.edu.
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, PR China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Central Arkansas Veterans Healthcare System, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Arkansas Veterans Healthcare System, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: MehtaJL@uams.edu.
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E
keywords: Autophagy; Inflammation; LOX-1; Shear stress