Macro-porosity is necessary for the reduction of neointimal and medial thickening by external stenting of porcine saphenous vein bypass grafts

BACKGROUND: placing external non-restrictive macro-porous stents around porcine vein grafts prevents neointima formation and medial thickening in both the short and long term. Whether the porosity of the stent material influences this effect, however, has not been determined. Therefore, the effect on neointimal and medial thickening of external macro-porous (polyester) and micro-porous (polytetrafluorethylene) stents of equal diameter were compared. The effect on expression of platelet-derived growth factor (PDGF), a potent mediator of vascular smooth muscle cell migration and proliferation and its receptors was also investigated. METHODS AND RESULTS: saphenous vein-carotid artery interposition grafting was performed in Landrace pigs with external placement of 8 mm diameter macro- and micro-porous stents contralaterally. One month after surgery, graft wall dimensions, PDGF and PDGF receptor expression and cell proliferation using proliferating cell nuclear antigen (PCNA) were measured on histological sections. Macro-porous stents significantly reduced neointimal and medial thickening compared with micro-porous stents (0.1+/-0.02 vs. 0.25+/-0.03 mm, P<0.002, and 0.10+/-0.02 vs. 0.17+/-0.02 mm, P<0.014, respectively). Macro-porous stents significantly reduced the percentage of cells expressing PDGF and PCNA, compared with micro-porous stents (36+/-9 vs. 80+/-7, P < 0.002, and 11+/-3 vs. 21+/-2, P < 0.02, respectively). The percentage of cells expressing PDGF receptors was similar with both the stent types. Adventitial microvessel formation occurred across macro-porous stents but was markedly suppressed by micro-porous stents. CONCLUSIONS: porosity is crucial to the efficacy of external stents in reducing neointima formation in porcine vein grafts. Decreases in PDGF expression and cell proliferation accompany the reduction in neointima formation. In addition, macro-porous stents allow adventitial microvessels to connect with the vasculature outside the stent, thereby potentially improving oxygenation. Although external stenting is highly effective in reducing neointima formation after vein grafting, the properties of the stent material necessary for this effect have not been defined. This study establishes that macro-porosity is one essential feature required to reduce PDGF expression cell proliferation and neointima formation.