External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting

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Abstract
Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited1,2. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis3. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors4–6, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF)7. Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation8. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation9. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.