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

Abstract

AimsDespite 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 resultsWe 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.ConclusionOur data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease.

5-Methoxyleoligin, a Lignan from Edelweiss, Stimulates CYP26B1-Dependent Angiogenesis In Vitro and Induces Arteriogenesis in Infarcted Rat Hearts In Vivo

“…Human umbilical vein endothelial cells (HUVECs) and smooth muscle cells were purchased from Promocell (Vienna, Austria) and cultured as previously described [15], [16].…”

The role of a group leader in a surgical research laboratory and his environment – a personal view

“…Another field of research that clearly falls into ''surgical research'' is the analysis of pathophysiological processes that either, make a surgical treatment necessary, or the analysis of unfavourable processes that occur after surgery. Since both fields also include the prevention and treatment of these processes, both may also result in a reduction of surgical interventions [1][2][3][4]. In many fields of surgery classical surgical procedures have been replaced with minimally invasive alternatives (e.g.…”

“…in the search for inhibitors of enzymes, which however significantly reduced the quality of model systems regarding their in vivo relevance. The university research laboratory is hardly able to compete with high throughput and high financial input research of industry but has the tremendous advantage -and this is particularly true for surgical research laboratories -of being close to patients, having easy access to human samples, and being able to work on complex, close-to-in vivo model systems, which significantly increases the relevance of the data generated [3,5,6]. In addition the university laboratory has a strong background in knowledge, as it may be the laboratory itself working on pathophysiologies and revealing significant and new factors responsible for diseases [2,5,[7][8][9][10][11][12][13][14][15][16][17].…”

“…The former is primarily a concept intended to analyse novel potential therapies [3,4,8,[18][19][20][21][22], may however also include e.g. the in vivo assessment of potential risk factors for diseases (e.g.…”

“…Compounds that may be highly relevant for surgical disciplines are drugs that stimulate wound healing, promote angiogenesis, inhibit hyperplasia (e.g. in bypass surgery [3]) etc. Other research fields that are highly related to surgical treatments i.e.…”