title: An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.
abstract: OBJECTIVE
  Current understanding of shear-sensitive signaling pathways has primarily been studied in vitro largely because of a lack of adequate in vivo models. Our objective was to develop a simple and well-characterized murine aortic coarctation model to acutely alter the hemodynamic environment in vivo and test the hypothesis that endothelial inflammatory protein expression is acutely upregulated in vivo by low-magnitude oscillatory wall shear stress (WSS).
  
  
  RESULTS
  Our model uses the shape memory response of nitinol clips to reproducibly induce an aortic coarctation and allow subsequent focal control over WSS in the aorta. We modeled the corresponding hemodynamic environment using computational fluid dynamics and showed that the coarctation produces low-magnitude oscillatory WSS distal to the clip. To assess the biological significance of this model, we correlated WSS to inflammatory protein expression and fatty streak formation. Vascular cell adhesion molecule-1 expression and fatty streak formation were both found to increase significantly in regions corresponding to acutely induced low-magnitude oscillatory WSS.
  
  
  CONCLUSIONS
  We have developed a novel aortic coarctation model that will be a useful tool for analyzing the in vivo molecular mechanisms of mechanotransduction in various murine models.
authors: Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Nick J
authors: NJ
authors: Willett
authors: Robert C
authors: RC
authors: Long
authors: Kathryn
authors: K
authors: Maiellaro-Rafferty
authors: Roy L
authors: RL
authors: Sutliff
authors: Richard
authors: R
authors: Shafer
authors: John N
authors: JN
authors: Oshinski
authors: Don P
authors: DP
authors: Giddens
authors: Robert E
authors: RE
authors: Guldberg
authors: W Robert
authors: WR
authors: Taylor
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001017:Aortic Coarctation / Q000378:metabolism / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D033081:Shear Strength; D015398:Signal Transduction; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1