An in vivo murine model of low-magnitude oscillatory wall shear stress to address the molecular mechanisms of mechanotransduction--brief report.
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.
Willett
Nick J
NJ
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Long
Robert C
RC
Maiellaro-Rafferty
Kathryn
K
Sutliff
Roy L
RL
Shafer
Richard
R
Oshinski
John N
JN
Giddens
Don P
DP
Guldberg
Robert E
RE
Taylor
W Robert
WR
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*
D019010:Vascular Cell Adhesion Molecule-1