CHRONIC SHEAR STRESS EFFECTS ON ENDOTHELIAL CELL RESPONSE

Type of Document Dissertation
Author Elhadj, Selim
Author's Email Address elhadj@vt.edu
URN etd-12112001-133454
Title CHRONIC SHEAR STRESS EFFECTS ON ENDOTHELIAL CELL RESPONSE
Degree PhD
Department Chemical Engineering
Advisory Committee
Advisor Name Title
Kimberly E. Forsten Committee Chair
Aaron Goldstein Committee Member
R. Micheal Akers Committee Member
Rick Howard Committee Member
William H. Velander Committee Member
Keywords

* IGF-binding proteins
* IGF-I
* shear stress
* proteoglycans
* endothelial cells
* strain

Date of Defense 2001-12-10
Availability unrestricted
Abstract

The overall focus of this dissertation is on how chronic shear stress alters the

synthesis and secretion of important regulatory molecules by endothelial cells.

Our hypothesis was that inclusion of chronic pulsatile shear stress in our model

would lead to changes in endothelial cell release of regulatory molecules. We

distinguished between high arterial shear stresses and low venous shear stresses

and used static cell cultures as reference. The first part of this research

thus entailed the complete characterization of the flow dynamics in our

experimental biomechanical model. Cell stretching can have a physiological

effect on endothelial cells; hence we implemented a laser based optical

technique for real time strain measurement of the growth fibers used in our

culture system, and found that no significant strains were occurring during

shear treatment. After characterization of the mechanical environment of the

cells, we focused the scope of our research on metabolism of proteoglycans and

insulin-like growth factor-I (IGF-I) and related IGF binding proteins (IGFBPs)

in bovine aortic endothelial cells cultured under chronic pulsatile shear. We

found that shear stress increased the release of proteoglycans and significantly

altered proteoglycans distribution. We also found that there was an inverse

relationship between the shear level treatment used to obtain the purified

proteoglycans from endothelial cells and their potency in inhibiting

coagulation. IGF-I release and message (IGF-I mRNA) was decreased at high shear

stress compared to low shear stress. Further, the levels found under shear were

significantly greater than those observed in the static cell culture model.

IGFBPs released were also significantly increased by shear. This research thus

establishes a link between chronic pulsatile shear stress and the metabolism of

both primary (IGF-I) and secondary (IGFBPs, proteoglycans) regulators of

vascular cell activity. The improved realism of our experimental biomechanical

model has proved to be a valuable tool in improving the relevance of this study

to vascular research. Ultimately, this research calls for further investigation

in the molecular mechanisms underlying the phenomenological effects documented,

which may help in understanding fundamental aspects in cardiovascular disease

and its link to hemodynamics but our work is an important first step.

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