Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4– and TGF-β1–Dependent Pathway

DOI Web Site 被引用文献4件
  • Philippe Sucosky
    From the Department of Aerospace and Mechanical Engineering (P.S.), University of Notre Dame, Ind; the Wallace H. Coulter Department of Biomedical Engineering (P.S., K.B., A.P.Y.) and the School of Physics (A.E.), Georgia Institute of Technology, Atlanta, Ga; and the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.
  • Kartik Balachandran
    From the Department of Aerospace and Mechanical Engineering (P.S.), University of Notre Dame, Ind; the Wallace H. Coulter Department of Biomedical Engineering (P.S., K.B., A.P.Y.) and the School of Physics (A.E.), Georgia Institute of Technology, Atlanta, Ga; and the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.
  • Adnan Elhammali
    From the Department of Aerospace and Mechanical Engineering (P.S.), University of Notre Dame, Ind; the Wallace H. Coulter Department of Biomedical Engineering (P.S., K.B., A.P.Y.) and the School of Physics (A.E.), Georgia Institute of Technology, Atlanta, Ga; and the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.
  • Hanjoong Jo
    From the Department of Aerospace and Mechanical Engineering (P.S.), University of Notre Dame, Ind; the Wallace H. Coulter Department of Biomedical Engineering (P.S., K.B., A.P.Y.) and the School of Physics (A.E.), Georgia Institute of Technology, Atlanta, Ga; and the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.
  • Ajit P. Yoganathan
    From the Department of Aerospace and Mechanical Engineering (P.S.), University of Notre Dame, Ind; the Wallace H. Coulter Department of Biomedical Engineering (P.S., K.B., A.P.Y.) and the School of Physics (A.E.), Georgia Institute of Technology, Atlanta, Ga; and the Wallace H. Coulter Department of Biomedical Engineering and the Division of Cardiology (H.J.), Emory University, Atlanta, Ga.

説明

<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> Hemodynamics has been associated with aortic valve (AV) inflammation, but the underlying mechanisms are not well understood. Here we tested the hypothesis that altered shear stress conditions stimulate the expression of cytokines and adhesion molecules in AV leaflets via a bone morphogenic protein (BMP)- and transforming growth fact (TGF)-β1–dependent pathway. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> The ventricularis or aortic surface of porcine AV leaflets were exposed for 48 hours to unidirectional pulsatile and bidirectional oscillatory shear stresses ex vivo. Immunohistochemistry was performed to detect expressions of the 4 inflammatory markers VCAM-1, ICAM-1, BMP-4, and TGF-β1. Exposure of the aortic surface to pulsatile shear stress (altered hemodynamics), but not oscillatory shear stress, increased expression of the inflammatory markers. In contrast, neither pulsatile nor oscillatory shear stress affected expression of the inflammatory markers on the ventricularis surface. The shear stress–dependent expression of VCAM-1, ICAM-1, and BMP-4, but not TGF-β1, was significantly reduced by the BMP inhibitor noggin, whereas the TGF-β1 inhibitor SB431542 blocked BMP-4 expression on the aortic surface exposed to pulsatile shear stress. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> The results demonstrate that altered hemodynamics stimulates the expression of AV leaflet endothelial adhesion molecules in a TGF-β1– and BMP-4–dependent manner, providing some potential directions for future drug-based therapies for AV diseases. </jats:p>

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