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Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins
Authors:Thomas Schachner   Christina Steger   Simone Heiss   Nikolaos Bonaros   William Sterlacci   Guenther Laufer  Johannes Bonatti
Affiliation:

aDepartment of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria

bDepartment of Pathology, Innsbruck Medical University, Innsbruck, Austria

cBezirkskrankenhaus Hall in Tirol, Hall, Austria

Abstract:
Background: Paclitaxel exerts antiproliferative properties by stabilizing microtubuli of the cell. The substance is in clinical use for drug-eluting coronary stents. We aimed to test the hypothesis that paclitaxel treatment can reduce neointimal hyperplasia in cultured human saphenous veins and thus might be useful for local pharmacologic treatment of vein grafts prior to coronary artery bypass grafting (CABG). Methods: The remnants of saphenous veins from 13 patients undergoing CABG were collected. The development of neointimal hyperplasia was induced using an established organ culture model (incubation time 2 weeks). In the treatment group, paclitaxel was added to the culture medium at different concentrations. Results: Veins treated with 1 μmol/l paclitaxel showed a median increase of intimal thickness of 2 μm (range −76 to 46) above baseline levels, whereas untreated control veins increased by 15 μm (range −3 to 142) (p = 0.022). Treatment with 10 μmol/l paclitaxel resulted in a lower intimal thickness growth of 1 μm (range −82 to 212) above baseline levels (p = 0.035 vs controls). Treatment with 25 or 50 μmol/l paclitaxel did not further inhibit intimal hyperplasia. The neointimal amount of the contractile protein smooth muscle actin (SMA) in paclitaxel 1 μmol/l treated veins was significantly higher than baseline values (p = 0.037). The cytoskeletal protein desmin was predominant in the media, whereas it was less frequently found in the intima, and we observed no difference between controls and paclitaxel treated veins. The proliferation marker ki-67 was occasionally present in the circumferential media, whereas it was almost absent in both the (inner) longitudinal media and the intima. Elastic fibers were present in the media and intima before and after organ culture without significant differences between the groups. Collagen fibers (Masson's trichrome) were found abundantly (80%) in the inner longitudinal media, less commonly (20%) in the outer circumferential media, and they were absent in the intima without difference between the groups. Conclusion: Local paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins, without changing the amount of elastic or collagen fibers. Paclitaxel treatment leads to an increased amount of the contractile protein SMA and thus might have a therapeutic potential for the prevention of vein graft disease.
Keywords:Vein graft   Neointima   Intimal hyperplasia   Saphenous vein   Coronary surgery   Paclitaxel
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