Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Mechanical and Materials Engineering

Supervisor(s)

Dr. Eric Savory

Abstract

Cardiovascular diseases (CVDs) are the number one cause of death globally. Arterial endothelial cell (EC) dysfunction plays a key role in many of these CVDs, such as atherosclerosis. Blood flow-induced wall shear stress (WSS), among many other pathophysiological factors, is shown to significantly contribute to EC dysfunction.

The present dissertation is an in vitro investigation of quantified WSS on ECs to quantitatively analyze the EC morphometric parameters, as well as cytoskeletal remodeling.

A hemodynamic facility based on the parallel plate flow chamber (PPFC) concept. The Laser Doppler Velocimetry (LDV) method with a custom set-up was implemented to suit the needs of the small-scale channel flow measurements.

The effects of four different flow cases including the low steady laminar (LSL), medium steady laminar (MSL), non-zero-mean sinusoidal laminar (NZMSL), laminar carotid (LCRD) on EC area, perimeter, shape index (S.I.), angle of orientation, F-actin bundle remodeling and PECAM-1 re-distribution were studied. The S.I. and angle of orientation were found to be the most flow-sensitive morphometric parameters. A 2D FFT based image processing technique was applied to analyze the F-actin directionality and an alignment index (A.I.) was defined accordingly. For the first time, a (linear) mathematical relationship was proposed, based on the current findings, between the cell orientation vs. F-actin alignment. Also, for the first time, a significant peripheral loss of PECAM-1 in ECs subjected to athero-prone cases (LSL and NZMSL) with high internalization of this protein is reported, which might shed light on the mechanosensory role of PECAM-1 in mechanotransduction.

The present dissertation is an in vitro investigation of quantified WSS on ECs to quantitatively analyze the EC morphometric parameters, as well as cytoskeletal remodeling.

A hemodynamic facility based on the parallel plate flow chamber (PPFC) concept, with test section dimensions of 22 × 17.5 × 1.8 mm (L × W × H =length, width and height, respectively), capable of producing a wide range of physiologically relevant conditions was developed. The Laser Doppler Velocimetry (LDV) method with a custom set-up was implemented to suit the needs of the small-scale channel flow measurements.

The effects of four different flow cases including the low steady laminar (LSL), medium steady laminar (MSL), non-zero-mean sinusoidal laminar (NZMSL), laminar carotid (LCRD) on EC area, perimeter, shape index (S.I.), angle of orientation, F-actin bundle remodeling and PECAM-1 re-distribution were studied. The S.I. and angle of orientation were found to be the most flow-sensitive morphometric parameters. A 2D FFT based image processing technique was applied to analyze the F-actin directionality and an alignment index (A.I.) was defined accordingly. For the first time, a (linear) mathematical relationship was proposed, based on the current findings, between the cell orientation vs. F-actin alignment. Also, for the first time, a significant peripheral loss of PECAM-1 in ECs subjected to athero-prone cases (LSL and NZMSL) with high internalization of this protein is reported, which might shed light on the mechanosensory role of PECAM-1 in mechanotransduction.


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