© 2000 American Heart Association, Inc.
Vascular Biology |
Mouse Model of Transplant Arteriosclerosis
Role of Intercellular Adhesion Molecule-1
From the Institute for General and Experimental Pathology (H.D., Y.H., G.W.), University of Innsbruck Medical School; the Institute for Biomedical Aging Research (Y.Z., G.W., Q.X.), Austrian Academy of Sciences; and the Departments of Pathology (S.D.) and Internal Medicine (R.K.), University of Innsbruck Medical School, Innsbruck, Austria.
Correspondence to Dr Qingbo Xu, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail Qingbo.Xu{at}oeaw.ac.at
Abstract—Transplant-accelerated
arteriosclerosis in coronary arteries is
the major limitation to long-term survival of patients with heart
transplantation. The pathogenesis of this disease is not fully
understood. Herein, we describe a simplified model of artery allografts
in the mouse that allows us to take advantage of transgenic, knockout,
or mutant animals. Common carotid arteries or aortic vessels were
end-to-end allografted into carotid arteries between C57BL/6J and
BALB/c mice. Neointimal lesions were observed as early as 2
weeks after surgery and had progressed at 4 and 6 weeks
postoperatively. The lumen of grafted arteries was significantly
narrowed due to neointima hyperplasia 4 weeks after
transplantation. Using this model, we studied the role of intercellular
adhesion molecule-1 (ICAM-1) in the development of transplant
arteriosclerosis in ICAM-1–deficient mice.
Neointimal lesions of artery grafts from ICAM-1 –/–
C57BL/6J to BALB/c mice were reduced up to 60% compared with wild-type
controls. MAC-1 (CD11b/18)-positive cells adhering to the surface of
ICAM-1 –/– artery grafts were significantly less as identified by en
face immunofluorescence, and these positive cells
were more abundant in intimal lesions of artery grafts in wild-type
mice. Furthermore, the major cell component of neointimal
lesions 4 weeks after surgery was found to be 
-actin–positive
smooth muscle cells, which were significantly reduced in lesions of
ICAM-1 –/– artery grafts. Thus, this model has been proven to be
useful for understanding the mechanism of transplant
arteriosclerosis. Our findings demonstrate that
ICAM-1 is critical in the development of allograft
arteriosclerosis via mediation of leukocyte
adhesion to, and infiltration into, the vessel wall.
Key Words: transplant arteriosclerosis • mouse models • ICAM-1 deficiency
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