An In Vivo Murine Model of Low Magnitude Oscillatory Wall Shear Stress to Address the Molecular Mechanisms of Mechanotransduction

• Type of Material: Article
• Authors: Nick J. Willett, Emory University; Robert Long Jr., Emory University; Kathryn Maiellaro-Rafferty, Emory University; Roy Sutliff, Emory University; Richard Schafer, Georgia Institute of Technology; John Oshinski, Emory University; Don P Giddens, Emory University; Robert E. Guldberg, Emory University; W Robert Taylor, Emory University
• Language: English
• Date: 2010-11
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 American Heart Association, Inc. All rights reserved.
• Final Published Version (URL): http://atvb.ahajournals.org/content/30/11/2099
• Title of Journal or Parent Work: Arteriosclerosis, Thrombosis, and Vascular Biology
• ISSN: 1079-5642
• Volume: 30
• Issue: 11
• Start Page: 2099
• End Page: 2102
• Grant/Funding Information: This work was supported by NIH RO1 HL70531, NIH RO1 HL090584, NIH UO1 HL080711and a predoctoral research fellowship from the Southeast Affiliate of the American heart Association.
• Keywords: Wall Shear Stress; Atherosclerosis; Mechanotransduction; Murine Model; Coarctation
• Research Categories: Health Sciences, Radiology; Engineering, Biomedical

Abstract

Objective Current understanding of shear sensitive signaling pathways has primarily been studied in vitro largely due to 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 in by low magnitude oscillatory WSS. Methods and Results Our model utilizes 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. VCAM-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.