title: Flow shear stress affects macromolecular accumulation through modulation of internal elastic lamina fenestrae.
abstract: BACKGROUND
  Internal elastic lamella and elastic lamellae serve as barriers for macromolecular accumulation in vascular wall. The function of internal elastic lamella in atherogenesis induced by shear stress has not been well understood yet. In the present study, internal elastic lamella remodeling and transmural accumulation of macromolecules in the arterial wall under altered shear stress were investigated.
  
  
  METHODS
  The ligation of left distal carotid branches induced low shear stress in the left common carotid artery and high shear stress in the right common carotid artery of rats for 7 days. Fenestrae in internal elastic lamella were assessed by confocal microscopy. Horseradish peroxidase accumulation was determined by its transmural concentration profiles. Fibronectin expression was examined by immunohistologic staining and Western blotting.
  
  
  RESULTS
  Low shear stress significantly decreased the percentage of fenestrae area in internal elastic lamella from 15.35% to 8.03% in left common carotid artery, while high shear stress nearly had no influence in right common carotid artery. Comparing with less accumulation of horseradish peroxidase in right common carotid artery, horseradish peroxidase was significantly accumulated in the innermost part of the media, and fibronectin expression increased to 3.3-fold in left common carotid artery.
  
  
  CONCLUSIONS
  Our results suggested that shear stress alteration could influence the endothelial cell function as well as internal elastic lamella and elastic lamellae remodeling. Low shear stress decreased the permeability of internal elastic lamella and elastic lamellae by reducing fenestrae of them, which involved the enhanced fibronectin expression. Therefore, the increased accumulation of macromolecules in the arterial wall was observed. Our data supply new evidence on the mechanisms of atherogenesis induced by low shear stress.
authors.affiliation: Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, P.O. Box 888, Shanghai Jiao Tong University, 800 Dong Chuan Road, Minhang, Shanghai 200240, China.
authors.forename: Zi-Yi
authors.initials: ZY
authors.lastname: Guo
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yan
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Zhang
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D002339:Carotid Arteries / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033081:Shear Strength
chemical_list: D005353:Fibronectins; D006735:Horseradish Peroxidase