HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas Schachner Nikolaos Bonaros Johannes Bonatti Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schachner, T. Articles by Bonatti, J. Search for Related Content PubMed PubMed Citation Articles by Schachner, T. Articles by Bonatti, J. Related Collections Coronary disease Molecular biology

Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins

^a Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria
^b Department of Pathology, Innsbruck Medical University, Innsbruck, Austria
^c Bezirkskrankenhaus Hall in Tirol, Hall, Austria

Received 27 March 2007; received in revised form 7 September 2007; accepted 10 September 2007.

^_* Corresponding author. Address: Department of Cardiac Surgery, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Tel.: +43 512 5040; fax: +43 512 504 22528. (Email: Thomas.Schachner{at}i-med.ac.at).

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.

Key Words: Vein graft • Neointima • Intimal hyperplasia • Saphenous vein • Coronary surgery • Paclitaxel