Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1.
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 alpha-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.
Dietrich
H
H
Institute for General and Experimental Pathology, University of Innsbruck Medical School, Austria.
Hu
Y
Y
Zou
Y
Y
Dirnhofer
S
S
Kleindienst
R
R
Wick
G
G
Xu
Q
Q
D000199:Actins / Q000378:metabolism; D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000601:surgery; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery; D003324:Coronary Artery Disease / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000009:adverse effects*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology
D000199:Actins; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1