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建立一个数学模型来描述单核细胞趋化蛋白-1 通过三维胶原基质的传输。

Development of a mathematical model to describe the transport of monocyte chemoattractant protein-1 through a three-dimensional collagen matrix.

机构信息

School of Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078, USA.

出版信息

Cardiovasc Pathol. 2012 May-Jun;21(3):219-28. doi: 10.1016/j.carpath.2011.09.002. Epub 2011 Nov 18.

Abstract

INTRODUCTION

Monocyte chemoattractant protein-1 is a bioactive molecule that is expressed in significant amounts in all stages of atherosclerosis. The role of monocyte chemoattractant protein-1 in this disease is to recruit monocytes across the endothelium and into the arterial tissue. Eventually, the monocytes differentiate into cholesterol-engorged macrophages called "foam cells" that result in atherosclerotic plaque formation. The mechanism that monocyte chemoattractant protein-1 uses to mediate monocyte transendothelial migration is believed to be via its concentration gradient. However, the formation of the monocyte chemoattractant protein-1 concentration gradient in the extracellular matrix is still poorly understood.

METHODS

A three-dimensional in vitro vascular tissue model has been developed to study the cellular mechanisms involved in the early stages of atherosclerosis. In the present study, a mathematical model is used to determine the gradient of monocyte chemoattractant protein-1 in the collagen matrix of the three-dimensional in vitro vascular tissue model. Experiments were performed to investigate the stability of monocyte chemoattractant protein-1 and the interaction between monocyte chemoattractant protein-1 and the collagen matrix.

RESULTS AND CONCLUSIONS

Monocyte chemoattractant protein-1 is stable for at least 24 h under experimental conditions and monocyte chemoattractant protein-1 interacts with the collagen matrix. The diffusion coefficient for the transport of monocyte chemoattractant protein-1 in the collagen matrix and the rate constant for the binding of monocyte chemoattractant protein-1 to collagen were determined to be 0.108 mm(2) h(-1) and 0.858 h(-1), respectively. Numerical results from the model indicate that the concentration gradients of both soluble and matrix-bound (or static) monocyte chemoattractant protein-1 are formed inside the collagen matrix.

摘要

简介

单核细胞趋化蛋白-1 是一种生物活性分子,在动脉粥样硬化的所有阶段都大量表达。单核细胞趋化蛋白-1 在这种疾病中的作用是招募单核细胞穿过内皮进入动脉组织。最终,单核细胞分化为富含胆固醇的巨噬细胞,称为“泡沫细胞”,导致动脉粥样硬化斑块形成。单核细胞趋化蛋白-1 介导单核细胞穿过内皮迁移的机制被认为是通过其浓度梯度。然而,细胞外基质中单核细胞趋化蛋白-1 浓度梯度的形成仍知之甚少。

方法

已经开发了一种三维体外血管组织模型来研究参与动脉粥样硬化早期阶段的细胞机制。在本研究中,使用数学模型来确定三维体外血管组织模型胶原基质中单核细胞趋化蛋白-1 的梯度。进行实验以研究单核细胞趋化蛋白-1 的稳定性以及单核细胞趋化蛋白-1 与胶原基质的相互作用。

结果和结论

在实验条件下,单核细胞趋化蛋白-1 至少稳定 24 小时,并且单核细胞趋化蛋白-1 与胶原基质相互作用。在胶原基质中运输单核细胞趋化蛋白-1 的扩散系数和单核细胞趋化蛋白-1 与胶原结合的速率常数分别确定为 0.108 mm(2) h(-1)和 0.858 h(-1)。模型的数值结果表明,可溶性和基质结合(或静态)单核细胞趋化蛋白-1 的浓度梯度都在胶原基质内部形成。

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