Paclitaxel treatment reduces neointimal hyperplasia in cultured human saphenous veins.
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 micromol/l paclitaxel showed a median increase of intimal thickness of 2 microm (range -76 to 46) above baseline levels, whereas untreated control veins increased by 15 microm (range -3 to 142) (p=0.022). Treatment with 10 micromol/l paclitaxel resulted in a lower intimal thickness growth of 1 microm (range -82 to 212) above baseline levels (p=0.035 vs controls). Treatment with 25 or 50 micromol/l paclitaxel did not further inhibit intimal hyperplasia. The neointimal amount of the contractile protein smooth muscle actin (SMA) in paclitaxel 1 micromol/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.


CONCLUSIONS
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.
Schachner
Thomas
T
Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. Thomas.Schachner@i-med.ac.at
Steger
Christina
C
Heiss
Simone
S
Bonaros
Nikolaos
N
Sterlacci
William
W
Laufer
Guenther
G
Bonatti
Johannes
J
D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001026:Coronary Artery Bypass; D003893:Desmin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D004547:Elastic Tissue / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D017239:Paclitaxel / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050257:Tubulin Modulators / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000199:Actins; D003893:Desmin; D019394:Ki-67 Antigen; D050257:Tubulin Modulators; D017239:Paclitaxel