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Inhibition of accelerated atherosclerosis in vein grafts by placement of external stent in ApoE*3-Leiden transgenic mice

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Author: Lardenoye, J.H.P. · Vries, M.R. de · Grimbergen, J.M. · Havekes, L.M. · Knaapen, M.W.M. · Kockx, M.M. · Hinsbergh, V.W.M. van · Bockel, J.H. van · Quax, P.H.A.
Institution: Gaubius Instituut TNO
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 9, 22, 1433-1438
Identifier: 236665
doi: doi:10.1161/01.ATV.0000030339.79524.6E
Keywords: Animals · Apolipoprotein E3 · Apolipoproteins E · Arteriosclerosis · Carotid Arteries · Disease Progression · Endothelium, Vascular · Foam Cells · Graft Occlusion, Vascular · Hypercholesterolemia · Male · Mice · Mice, Inbred C57BL · Mice, Transgenic · Stents · Tunica Intima · Veins


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. Chemicals/CAS: apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E