This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 97/5/450    most recent 01.RES.0000181026.94390.c9v1 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, K. Articles by Penn, M. S. Search for Related Content PubMed PubMed Citation Articles by Lee, K. Articles by Penn, M. S. Related Collections Pathophysiology Mechanism of atherosclerosis/growth factors

(Circulation Research. 2005;97:450.)
© 2005 American Heart Association, Inc.

Cellular Biology

Alterations in Internal Elastic Lamina Permeability As a Function of Age and Anatomical Site Precede Lesion Development in Apolipoprotein E–Null Mice

Kwangdeok Lee, Farhad Forudi, Gerald M. Saidel, Marc S. Penn

From the Department of Biomedical Engineering (K.L., G.M.S., M.S.P.), Case Western Reserve University, Cleveland; and Departments of Cardiovascular Medicine and Cell Biology (K.L., F.F., M.S.P.), Cleveland Clinic Foundation, Ohio.

Correspondence to Marc S. Penn, MD, PhD, Depts of Cardiovascular Medicine and Cell Biology, NC10, 9500 Euclid Ave, Cleveland, OH 44195. E-mail pennm{at}ccf.org

Early atherosclerosis is characterized by the accumulation of plasma-borne macromolecules (eg, low-density lipoproteins) in the arterial intima, which is bordered by endothelial cells (EC) and the internal elastic lamina (IEL). This accumulation is believed to be secondary to increased EC permeability. We hypothesized that a decrease in IEL permeability may precede lesion development and contribute to macromolecular accumulation. To test this hypothesis, we quantified EC and IEL permeability in lesion-free areas of the thoracic and abdominal aortas of chow-fed C57BL/6 control and atherosclerotic-prone apolipoprotein E (apoE)-null mice at 3 and 5 months of age. Between 3 and 5 months of age, apoE-null mice begin to develop atherosclerotic lesions in the thoracic aorta. No significant differences in EC and IEL permeability were observed at either time in C57BL/6 control mice. In contrast, 78% and 19% decreases in IEL permeability of the thoracic aorta and abdominal aorta, respectively, were observed between 3 to 5 months of age in apoE-null mice (thoracic: 2.05±1.33 and 0.44±0.15 µm/min, P<0.001; abdominal: 1.13±0.58 and 0.93±0.44 µm/min, P<0.05). To further determine whether decreased IEL permeability is linked with atherosclerotic lesion development, we quantified IEL permeability in the greater and lesser curvature of the aortic arch. In apoE-null mice, the lesser curvature of the aortic arch develops lesions before the greater curvature. We found a significant and sustained decrease (59%) in IEL permeability in the lesser curvature of the aortic arch compared with the greater curvature. These data suggest that atherogenesis involves the pathological remodeling of the IEL, not the endothelium before lesion development. This remodeling may be attributable to local responses of the endothelium and smooth muscle cells to hyperlipidemia.

Key Words: atherogenesis • extracellular matrix • mathematical modeling • endothelial dysfunction

This article has been cited by other articles:

				K. Lee, G. M. Saidel, and M. S. Penn Permeability change of arterial endothelium is an age-dependent function of lesion size in apolipoprotein E-null mice Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2273 - H2279. [Abstract] [Full Text] [PDF]