Mouse model of venous bypass graft arteriosclerosis.
Saphenous vein grafts are widely used for treatment of severe atherosclerosis via aortocoronary bypass surgery, a procedure often complicated by later occlusion of the graft vessel. Because the molecular mechanisms of this process remain largely unknown, quantitative models of venous bypass graft arteriosclerosis in transgenic mice could be useful to study this process at the genetic level. We describe herein a new model of vein grafts in the mouse that allows us to take advantage of transgenic, knockout, or mutant animals. Autologous or isogeneic vessels of the external jugular or vena cava veins were end-to-end grafted into carotid arteries of C57BL/6J mice. Vessel wall thickening was observed as early as 1 week after surgery and progressed to 4-, 10-, 15-, and 18-fold original thickness in grafted veins at age 2, 4, 8, and 16 weeks, respectively. The lumen of grafted veins was significantly narrowed because of neointima hyperplasia. Histological and immunohistochemical analyses revealed three lesion processes: marked loss of smooth muscle cells in vein segments 1 and 2 weeks after grafting, massive infiltration of mononuclear cells (CD11b/18+) in the vessel wall between 2 and 4 weeks, and a significant proliferation of vascular smooth muscle cells (alpha-actin+) to constitute neointimal lesions between 4 and 16 weeks. Similar vein graft lesions were obtained when external jugular veins or vena cava were isografted into carotid arteries of C57BL/6J mice. Moreover, no significant intima hyperplasia in vein-to-vein isografts was found, although there was leukocyte infiltration in the vessel wall. Thus, this model, which reproduces many of the features of human vein graft arteriosclerosis, should prove useful for our understanding of the mechanism of vein graft disease and to evaluate the effects of drugs and gene therapy on vascular diseases.
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck.
Y
Y
Zou
H
H
Dietrich
Y
Y
Hu
B
B
Metzler
G
G
Wick
Q
Q
Xu
D000714:Anastomosis, Surgical; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000601:surgery*; D002339:Carotid Arteries / Q000601:surgery; D001026:Coronary Artery Bypass; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D006083:Graft Occlusion, Vascular; D007601:Jugular Veins / Q000473:pathology / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D014680:Veins / Q000473:pathology; D014682:Vena Cava, Inferior / Q000473:pathology / Q000637:transplantation