HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/H2651    most recent 00332.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buijs, J. O. d. Articles by van Riel, N. Search for Related Content PubMed PubMed Citation Articles by Buijs, J. O. d. Articles by van Riel, N.

Mathematical modeling of vascular endothelial layer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening

¹Department of Biomedical Engineering and ²Department of Electrical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven; ³Department of Molecular Cell Biology, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht; and ⁴Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands

Submitted 6 April 2004 ; accepted in final form 27 July 2004

Maintenance of the endothelial cell (EC) layer of the vessel wall is essential for proper functioning of the vessel and prevention of vascular disorders. Replacement of damaged ECs could occur through division of surrounding ECs. Furthermore, EC progenitor cells (EPCs), derived from the bone marrow and circulating in the bloodstream, can differentiate into ECs. Therefore, these cells might also play a role in maintenance of the endothelial layer in the vascular system. The proliferative potential of both cell types is limited by shortening of telomeric DNA. Accelerated telomere shortening might lead to senescent vascular wall cells and eventually to the inability of the endothelium to maintain a continuous monolayer. The aim of this study was to describe the dynamics of EC damage and repair and telomere shortening by a mathematical model. In the model, ECs were integrated in a two-dimensional structure resembling the endothelium in a large artery. Telomere shortening was described as a stochastic process with oxidative damage as the main cause of attrition. Simulating the model illustrated that increased cellular turnover or elevated levels of oxidative stress could lead to critical telomere shortening and senescence at an age of 65 yr. The model predicted that under those conditions the EC layer could display defects, which could initiate severe vascular wall damage in reality. Furthermore, simulations showed that 5% progenitor cell homing/yr can significantly delay the EC layer defects. This stresses the potential importance of EPC number and function to the maintenance of vascular wall integrity during the human life span.

atherosclerosis; computer simulation; endothelial cells; progenitor cells

This article has been cited by other articles:

				Y. Wang, Y. Zheng, W. Zhang, H. Yu, K. Lou, Y. Zhang, Q. Qin, B. Zhao, Y. Yang, and R. Hui Polymorphisms of KDR Gene Are Associated With Coronary Heart Disease J. Am. Coll. Cardiol., August 21, 2007; 50(8): 760 - 767. [Abstract] [Full Text] [PDF]

				J. E. Deanfield, J. P. Halcox, and T. J. Rabelink Endothelial Function and Dysfunction: Testing and Clinical Relevance Circulation, March 13, 2007; 115(10): 1285 - 1295. [Full Text] [PDF]

				H. Chon, M. C. Verhaar, H. A. Koomans, J. A. Joles, and B. Braam Role of Circulating Karyocytes in the Initiation and Progression of Atherosclerosis Hypertension, May 1, 2006; 47(5): 803 - 810. [Abstract] [Full Text] [PDF]

				N. Werner, S. Kosiol, T. Schiegl, P. Ahlers, K. Walenta, A. Link, M. Bohm, and G. Nickenig Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes N. Engl. J. Med., September 8, 2005; 353(10): 999 - 1007. [Abstract] [Full Text] [PDF]