Abstract

The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process.

Highlights

  • Cardiovascular disease is a leading cause of mortality and hospitalization in North America [1]

  • Human abdominal aortic endothelial cells (HAAECs) were successfully cultured in both models

  • Under static conditions, the morphology of the cells in the three-dimensional models was similar to that seen in cell culture flasks

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Summary

Introduction

Cardiovascular disease is a leading cause of mortality and hospitalization in North America [1]. Atherosclerosis, a disease characterized by arterial wall fibrosis and lipid accumulation, occurs in elastic and large to medium size muscular arteries throughout the human vasculature, and is evident in regions of curvature and bifurcation [2] This focal predilection cannot be explained by lifestyle or genetic risk factors alone and has been linked to the response of endothelial cells (ECs) lining the luminal surface of blood vessels. Due to the difficulty of studying the endothelium in vivo, a number of in vitro systems have been developed with the aim of replicating the in vivo hemodynamics over a cultured monolayer of ECs in a controlled environment These models include: parallel plate chambers [4,5,6,7,8,9]; cone and plate viscometer systems [10,11,12,13,14]; and three-dimensional, straight, tubular flow models [15,16,17,18]. Most of these devices assume uniform shear stress and uniform cell response across the flow surface, allowing for easy quantification of average cell response

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