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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2288.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Modulation of Expression of Endothelial Intercellular Adhesion Molecule-1, Platelet–Endothelial Cell Adhesion Molecule-1, and Vascular Cell Adhesion Molecule-1 in Aortic Arch Lesions of Apolipoprotein E–Deficient Compared With Wild-Type Mice

Presented in part at the XVIIth International Society on Thrombosis and Hemostasis Congress, Washington, DC, August 14–21, 1999, and published in abstract form (Thromb Haemost. 1999;82[suppl 1]:344).

Kazem Zibara; Elza Chignier; Chantal Covacho; Robin Poston; Georges Canard; Patrick Hardy; John McGregor

From INSERM U331/Faculté de Médecine RTH Laënnec (K.Z., E.C., C.C., J.M.), Lyon, France; the Department of Experimental Pathology (R.P.), United Medical and Dental Schools of Guy’s and St. Thomas’ Hospitals, London, UK; and Transgenic Alliance (G.C., P.H.), Iffa Credo, L’Arbresle, France.

Correspondence to Kazem Zibara, PhD, INSERM U331, Faculté de Médecine RTH Laënnec, 8 rue Guillaume Paradin, F-69732 Lyon Cedex 08, France. E-mail zibara{at}laennec.univ-lyon 1.fr

Abstract—Human vascular adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), platelet–endothelial cell adhesion molecule-1 (PECAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are thought to play a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known about the expression of adhesion molecules in the vasculature of mice models, such as apolipoprotein E knockout (apoE^-/-) mice, the lesions of which closely mimic human atherosclerotic lesions. This study has first quantitatively characterized the mean expression of endothelial adhesion molecules, lining the whole vessel intimal circumference, over a period of time (0 to 20 weeks of diet) in aortic arch lesions of male apoE-deficient compared with wild-type (C57BL/6) mice. These animals were fed a chow or a cholesterol-rich diet. ApoE^-/- animals showed first an increase (at 6 weeks) and then a reduction (at 16 weeks) in the mean expression of ICAM-1 (P<0.05) and PECAM-1 (P<0.05) but not VCAM-1 levels. Such modulation of the mean expression of adhesion molecules was not observed in wild-type mice. Confirmation of immunohistochemistry results on ICAM-1 was obtained by Northern blots performed on the aortic arch of apoE and C57BL6 chow-fed mice over a period of 20 weeks. Moreover, the presence of VCAM-1 was also confirmed at the RNA level, on aortas of control and apoE mice, by reverse transcription–polymerase chain reaction. In the second part of the study, we assayed the levels of adhesion molecules, in different types of histologically defined atherosclerotic lesions, in apoE^-/- animals fed for 20 weeks. All 3 adhesion molecules (ICAM-1, PECAM-1, and VCAM-1) were observed to be reduced in fibrofatty and complex lesions but not in fatty streaks or in areas without lesions. These results indicate that the expression of these adhesion molecules in apoE-deficient animals varies with the evolution of the plaque from a fatty to a fibrous stage.

Key Words: atherosclerosis • adhesion molecules • apolipoprotein E–deficient mice • quantitative image analysis • Northern blots

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