0
RESEARCH PAPERS

A Mathematical Model for the Receptor Mediated Cellular Regulation of the Low Density Lipoprotein Metabolism

[+] Author and Article Information
F. Yuan, S. Weinbaum

Department of Mechanical Engineering, City College of City University of New York, New York, NY 10031

R. Pfeffer

Department of Chemical Engineering, City College of City University of New York, New York, NY 10031

S. Chien

Departments of AMES-Bioengineering and Medicine, University of California, San Diego, La Jolla, CA 92093

J Biomech Eng 113(1), 1-10 (Feb 01, 1991) (10 pages) doi:10.1115/1.2894079 History: Received June 01, 1990; Revised November 01, 1990; Online March 17, 2008

Abstract

A prototype mathematical model for Brown and Goldstein’s pioneering studies on the LDL receptor mediated pathway for the regulation of the cellular content of cholesterol has been developed in this paper. In order to analyze the essential features of this complex system quantitatively and still reflect the framework of the total system, six important processes are considered in the model. They are: (1A, B) the hydrolysis and synthesis of the LDL receptor; (2) the binding of LDL to its receptors; (3) the hydrolysis of LDL; (4) the storage of cholesteryl esters; (5) the regulation of de novo synthesis of cholesterol; and (6) the efflux of free cholesterol to the external medium. All these processes form a system to let the cells take up enough cholesterol from the external medium for their utilization and yet avoid the excessive accumulation of the lipid within the cells. The validity of the model is tested by showing that it can predict many of experimental curves obtained for human fibroblasts in tissue culture studies. The main purpose of the model is to determine how the free cholesterol level in the cell is related to the external LDL concentration and the regulatory capacity of the cells to adapt to a changing LDL environment. In addition, the model reveals an important behavior of SMC, i.e., for a slowly increasing LDL concentration in the extracellular medium, the rate of intracellular degradation of LDL will first increase and then become saturated. It is proposed based on these results that the saturation of LDL degradation by SMCs and the subsequent increase in subendothelial LDL levels in regions of high macromolecular permeability might play a vital role in the formation of the early foam cell lesion.

Copyright © 1991 by The American Society of Mechanical Engineers
Your Session has timed out. Please sign back in to continue.

References

Figures

Tables

Errata

Discussions

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In