Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts.

Abstract

AIMS:

Despite the lower patency of venous compared with arterial coronary artery bypass grafts, approximately 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.

• 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
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 82 Issue 3 Pg. 542-9 (Jun 01 2009) ISSN: 1755-3245 [Electronic] England
• PMID: 19228707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lignans
• Plant Extracts
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• leoligin
• Cyclin-Dependent Kinase Inhibitor p27

Topics

• Animals
• Asteraceae (chemistry)
• Blood Platelets (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• Endothelial Cells (drug effects)
• G1 Phase (drug effects)
• Graft Occlusion, Vascular (prevention & control)
• Humans
• Hyperplasia (prevention & control)
• In Vitro Techniques
• Lignans (isolation & purification, pharmacology, therapeutic use)
• Mice
• Myocytes, Smooth Muscle (drug effects)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Saphenous Vein (drug effects, pathology)
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Cell Adhesion Molecule-1 (metabolism)