Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts
Open Access
- 19 February 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 82 (3), 542-549
- https://doi.org/10.1093/cvr/cvp059
Abstract
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.). 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. 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.This publication has 34 references indexed in Scilit:
- The role of vein grafts in coronary surgeryEuropean Surgery, 2007
- Flaxseed and Its Lignans Inhibit Estradiol-Induced Growth, Angiogenesis, and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Xenografts In vivoClinical Cancer Research, 2007
- Honokiol causes the p21WAF1‐mediated G(1)‐phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cellsFEBS Letters, 2006
- In vivo (animal) models of vein graft disease☆European Journal of Cardio-Thoracic Surgery, 2006
- Lumen Loss in the First Year in Saphenous Vein Grafts Is Predominantly a Result of Negative Remodeling of the Whole Vessel Rather Than a Result of Changes in Wall ThicknessCirculation, 2006
- Perivascular Treatment with Azathioprine Reduces Neointimal Hyperplasia in Experimental Vein GraftsThe Heart Surgery Forum, 2006
- Cardiac Saphenous Vein Bypass Graft DiseaseSeminars in Vascular Medicine, 2004
- Disruption of vascular endothelial homeostasis by tobacco smoke—impact on atherosclerosisThe FASEB Journal, 2003
- Use of intravascular ultrasound for in vivo assessment of changes in intimal thickness of angiographically normal saphenous vein grafts one year after aortocoronary bypass surgery.Heart, 1996
- Saphenous vein biopsy: A predictor of vein graft failureJournal of Vascular Surgery, 1993