Matrigel-coated stents reduce intimal thickening in a large animal vascular stent model.
BACKGROUND
Restenosis within vascular stents is primarily due to intimal thickening secondary to intimal hyperplasia (IH) which occurs maximally around stent struts. Dedifferentiation of vascular smooth muscle cells (VSMC) with subsequent migration and proliferation is believed to be a key event in IH formation. Matrigel (basement membrane protein) has been shown to inhibit dedifferentiation of VSMC in vitro. Our aim was to test the in vivo effect of Matrigel on IH formation using a novel sheep vascular stent model.


METHODS
Twenty vascular stents were implanted in the renal arteries of ten sheep. The left renal artery of each sheep was used to deploy uncoated stent and the right renal artery was used to deploy Matrigel-coated stent. Five sheep were analysed at four weeks and five at eight weeks after stent implantation. The sheep were sacrificed at the end of the study periods and the stented renal artery segments were examined by histology. Luminal, intimal and medial areas were determined using computer-assisted morphometric analysis.


RESULTS
All stent sites were widely patent without thrombosis. No luminal stenosis was seen angiographically. IH was quantified from histology cross-sections and expressed as an intima to media (I/M) ratio. The ratio was significantly reduced in the matrigel-coated sites at eight weeks (uncoated 0.49+/-0.23; Matrigel-coated 0.32+/-0.12; p value <0.05).


CONCLUSIONS
The sheep renal artery vascular stent model is feasible for the study of stent biology. IH was reduced by Matrigel-coated stents.
Tso
C
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Department of Cardiology, Westmead Hospital, NSW, Australia.
Skinner
M P
MP
Hawthorne
W J
WJ
Fletcher
J P
JP
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D001672:Biocompatible Materials / Q000627:therapeutic use*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D003094:Collagen / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D007797:Laminin / Q000627:therapeutic use*; D011509:Proteoglycans / Q000627:therapeutic use*; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D012756:Sheep; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology / Q000601:surgery
D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen