Type
Text
Type
Dissertation
Advisor
Frame, Mary D | Clark, Richard | Rubenstein, David | Rosengart, Todd.
Date
2013-12-01
Keywords
arteriogenesis, ex vivo perfusion, monocyte, remodeling, wall shear stress | Biomedical engineering
Department
Department of Biomedical Engineering.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76987
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Background Vascular remodeling reestablishes blood flow in the case of occlusions and can save tissue that would otherwise become hypoxic and necrotic. Vascular growth in an adult can occur in two ways: angiogenesis and/or arteriogenesis. While some pathways that govern the two are similar, the triggers have been found to be distinct. This study focuses on arteriogenesis- believed to be triggered by increases in wall shear stress (WSS) due to arterial occlusion. Hypothesis Inflammatory response will be initiated in an ex vivo femoral artery model in response to an increase in WSS. The inflammatory response will be detected by increases in TNFα , MCP-1, IL-2, P-Selectin, ICAM-1 and VCAM-1 expression. Inflammation alone (TNFα or shear stress induced) is not sufficient to initiate collateral vessel growth; monocyte recruitment and adhesion are required to see changes in vasculogenic growth factors VEGF, FGF-2, TGFβ and Egr-1. Methodology C57BL/6 mice will be used in an in vivo femoral artery excision model to study inflammatory response, monocyte recruitment, and vascular remodeling over 3 days post-occlusion. Ex vivo studies will then use isolated perfused femoral artery to show the monocyte adhesion cascade and collateral vessel initiation under inflammatory conditions, specifically inflammation caused by an increase in vascular WSS. Results/Conclusions In vivo femoral artery excision (FAE) studies show significant increases in cytokines, adhesion molecules, monocytes and growth factors in the FAE samples over the contralateral. Inflammatory cytokines are expressed almost immediately after FAE in mouse. The resulting monocyte recruitment gives way to extravasation and proliferative arteriogenesis. The following ex vivo studies successfully defined a model for studying changes in WSS ex vivo, and show that the artery behaves by upregulating markers consistent with in vivo when subject to increases in WSS. Finally the perfusion of monocytes through the vessel results in adhesion when the endothelium is expressing inflammatory markers. The ex vivo femoral artery model can be used in future studies for longer time course analysis for vessel sprouting, as well as for studying inflammatory conditions initiated and treated in many different ways other than WSS. | 114 pages
Recommended Citation
Baldwin, Aparna Kadam, "An ex vivo femoral artery model to demonstrate inflammatory response and monocyte response following increased vascular wall shear stress" (2013). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2852.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2852