on July 18, 2002
Published online before print July 18, 2002, doi: 10.1161/01.ATV.0000030339.79524.6E
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Submitted on March 8, 2002
Accepted on June 25, 2002
Inhibition of Accelerated Atherosclerosis in Vein Grafts by Placement of External Stent in ApoE*3-Leiden Transgenic Mice
J. H.P. Lardenoye ;
From the Gaubius Laboratory TNO-PG (J.H.P.L., M.R.d.V., J.M.G., L.M.H., V.W.M.v.H., P.H.A.Q.) and the Leiden University Medical Center (J.H.P.L., J.H.v.B., P.H.A.Q.), Leiden, the Netherlands, and HistoGeneX (M.W.M.K., M.M.K.), Antwerp, Belgium.
* To whom correspondence should be addressed. E-mail: PHA.Quax{at}pg.tno.nl.
Objective—Vein grafts fail because of the development of intimal hyperplasia and accelerated atherosclerosis. Placement of an external stent around vein grafts resulted in an inhibition of intimal hyperplasia in several animal studies. Here, we assess the effects of external stenting on accelerated atherosclerosis in early vein grafts in carotid arteries in hypercholesterolemic apolipoprotein E*3-Leiden transgenic mice.
Methods and Results—Venous interposition grafting was performed in apolipoprotein E*3-Leiden mice fed standard chow or a highly cholesterol-rich diet for 4 weeks. After engraftment, external stents with different inner diameters (0.4 or 0.8 mm) were placed. In unstented vein grafts in hypercholesterolemic mice, thickening up to 50 times the original thickness, with foam cell--rich lesions, calcification, and necrosis, was observed within 28 days. The atherosclerotic lesions observed show high morphological resemblance to atherosclerotic lesions observed in human vein grafts. In stented vein grafts in hypercholesterolemic mice, no foam cell accumulation or accelerated atherosclerosis was observed. Compared with unstented vein grafts, stenting of vein grafts in a hypercholesterolemic environment resulted in a 94% reduction of vessel wall thickening. These effects were independent of stent size.
Conclusions—Extravascular stent placement results in strong inhibition of accelerated vein graft atherosclerosis in hypercholesterolemic transgenic mice and thereby provides a perspective for therapeutic intervention in vein graft diseases.
Key words: atherosclerosis • vein grafting • external stent • transgenic mice
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