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Animal Model |
From the Institute for Biomedical Aging Research,*
Austrian Academy of Sciences, and Institute for General and
Experimental Pathology,
University of
Innsbruck Medical School, Innsbruck, Austria
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 (
-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.
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