The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease

Farcas, Rouleau Leonie, Fraser Richard, Leask

Description

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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 4
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

BioMedical Engineering OnLine

BioMedCentral

Open Access Research The development of 3D,in vitro, endothelial culture models for the study of coronary artery disease 1 12 1 Monica A Farcas, Leonie Rouleau, Richard Fraserand Richard L Leask*

1 2 Address: Departmentof Chemical Engineering, McGill University, Montreal, Canada andDepartment of Pathology, McGill University, Montreal, Canada Email: Monica A Farcas  [e-mail]; Leonie Rouleau  [e-mail]; Richard Fraser  [e-mail]; Richard L Leask*  [e-mail] * Corresponding author

Published: 28 October 2009Received: 30 June 2009 Accepted: 28 October 2009 BioMedical Engineering OnLine2009,8:30 doi:10.1186/1475925X830 This article is available from: http://www.biomedicalengineeringonline.com/content/8/1/30 © 2009 Farcas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 idealizedin vitroflow chambers. Such cell culture models are unable to accurately replicate the complexin vivowall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realisticin vitroendothelial 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.

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 particularly evident in regions of curvature and bifurca

tion [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 lumi nal surface of blood vessels. It has been hypothesized that dysfunction of the endothelium leading to atherogenesis is stimulated by complex hemodynamic forces, such as wall shear stress [3].

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