title: Combined effects of physiologically relevant disturbed wall shear stress and glycated albumin on endothelial cell functions associated with inflammation, thrombosis and cytoskeletal dynamics.
abstract: OBJECTIVE
  Diabetes mellitus is a major risk factor in the development of cardiovascular diseases (CVDs). The presence of advanced glycation end-products (AGEs) promotes CVDs by upregulating endothelial cell (EC) inflammatory and thrombotic responses, in a similar manner as disturbed shear stress. However, the combined effect of disturbed shear stress and AGEs on EC function has yet to be determined. Our goal was to evaluate these effects on EC responses.
  
  
  METHODS
  ECs were incubated with AGEs for 5 days. ECs were then subjected to physiological or pathological shear stress. Cell metabolic activity, surface expression of intercellular adhesion molecule-1, thrombomodulin, connexin-43 and caveolin-1, and cytoskeleton organization were quantified.
  
  
  RESULTS
  The results show that irreversibly glycated albumin and pathological shear stress increased EC metabolic activity, and upregulated and downregulated the EC surface expression of intercellular adhesion molecule-1 and thrombomodulin, respectively. Expression of connexin-43, caveolin-1 and cytoskeletal organization was independent of shear stress; however, the presence of irreversibly glycated AGEs markedly increased connexin-43, and decreased caveolin-1 expression and actin cytoskeletal connectivity.
  
  
  CONCLUSIONS
  Our data suggest that irreversibly glycated albumin and disturbed shear stress could promote CVD pathogenesis by enhancing EC inflammatory and thrombotic responses, and through the deterioration of the cytoskeletal organization.
authors.affiliation: School of Mechanical and Aerospace Engineering Oklahoma State University Stillwater OK USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Maria
authors.affiliation: School of Mechanical and Aerospace Engineering Oklahoma State University Stillwater OK USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.affiliation: School of Mechanical and Aerospace Engineering Oklahoma State University Stillwater OK USA.
authors.forename: David Alan
authors.initials: DA
authors.lastname: Rubenstein
keywords: Advanced glycation end‐products; Cardiovascular disease; Shear stress