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: 295/6/H2273    most recent 00242.2008v1 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 Google Scholar Articles by Lee, K. Articles by Penn, M. S. PubMed PubMed Citation Articles by Lee, K. Articles by Penn, M. S.

Permeability change of arterial endothelium is an age-dependent function of lesion size in apolipoprotein E-null mice

¹Department of Biomedical Engineering, Case Western Reserve University; and ²Departments of Cardiovascular Medicine and Stem Cell Biology, NC10, Cleveland Clinic Foundation, Cleveland, Ohio

Submitted 7 March 2008 ; accepted in final form 28 September 2008

The remodeling process of the arterial wall in atherosclerosis involves intimal thickening, which can be related to the barrier functions of the endothelial cell layer (ECL) and internal elastic lamina (IEL) using horseradish peroxidase (HRP) as a tracer. To evaluate the ECL and IEL permeabilities (P_ECL and P_IEL, respectively) and intimal transport parameters, e.g., apparent HRP velocity (V_I) and diffusivity, we compared simulations with a mathematical model to experimental data. In this study, we injected HRP into the vein of apolipoprotein E-null mice and measured HRP concentration profiles in lesioned areas of aortas. Lesion size was characterized by lower, middle, and upper ranges of the intimal/medial thickness (_I/_M): 0 < _I/_M 0.5, 0.5 < _I/_M 1.0, and _I/_M > 1.0. The P_ECL (in micrometers per minute) of 5-mo-old mice in the middle range (0.98 ± 0.14) was significantly greater than that in the lower range (0.21 ± 0.03) but not significantly different from mice in the upper range (0.99 ± 0.55). The P_ECL of 12-mo-old mice increased significantly with the relative intimal thickness: 0.27 ± 0.04 in the lower range, 1.12 ± 0.15 in the middle range, and 1.74 ± 0.24 in the upper range. In both age groups, V_I (in micrometers per minute) increased significantly from lower to upper ranges of intimal thickness. However, P_IEL did not change significantly with relative intimal thickness and age. In the upper range of intimal thickness, P_ECL and V_I were significantly greater in 12-mo-old mice than in 5-mo-old mice. These data indicate an interaction between lesion growth and aging that leads to progressive loss in the integrity of the endothelial barrier function. Furthermore, the IEL is not a significant barrier between the intima and tunica media in the atherosclerotic process.

atherosclerosis; arterial wall transport; endothelial cell layer; intima