Year of Publication

2017

Degree Name

Master of Science in Biomedical Engineering

Document Type

Master's Thesis

College

Engineering

Department

Biomedical Engineering

First Advisor

Dr. Hainsworth Y. Shin

Abstract

Fluid pressures regulate endothelial cell (EC) tubulogenic activity involving fibroblast growth factor 2 (FGF-2) and its receptor, FGF receptor 2 (FGFR2). Our lab has recently shown that sustained 20 mmHg hydrostatic pressure (HP) upregulates EC sprout formation in a FGF2-dependent fashion. This upregulation of sprout formation may be due to enhanced FGF-2 / FGFR2 interactions in the presence of 20 mmHg HP. We hypothesize that exposure of ECs to 20 mmHg sustained HP enhances FGF-2 binding kinetics. We used a custom hydrostatic pressure system, immunofluorescence, and FACS to quantify FGF-2 binding by ECs in the absence or presence of a range of HPs for 30 minutes. Relative to cells maintained under control pressure, ECs exposed to 20, but neither 5 nor 40 mmHg, displayed a significant increase in binding affinity to FGF-2. EC binding of VEGF-A, another angiogenic growth factor, was unaffected by similar pressure stimuli. Additional studies showed that pressure-selective FGF-2 binding was independent of FGFR2 surface expression. These results implicate the FGF-2 axis in the pressure-sensitive, magnitude-dependent angiogenic processes which we have previously described. The present study provides novel insight regarding the involvement of FGF-2 signaling and interstitial pressure changes in various microvascular physiological and pathobiological processes.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2017.395

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