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- Title
Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts.
- Authors
Ute Reisinger; Stefan Schwaiger; Iris Zeller; Barbara Messner; Robert Stigler; Dominik Wiedemann; Tobias Mayr; Christoph Seger; Thomas Schachner; Verena M. Dirsch; Angelika M. Vollmar; Johannes O. Bonatti; Hermann Stuppner; Günther Laufer; David Bernhard
- Abstract
: Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). : Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. : Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease.
- Subjects
LIGNANS; EDELWEISS; HYPERPLASIA; CORONARY artery bypass; SAPHENOUS vein; MEDICAL screening; VASCULAR grafts; THERAPEUTICS
- Publication
Cardiovascular Research, 2009, Vol 82, Issue 3, p542
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvp059