5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo

Barbara Messner; Johann Kern; Dominik Wiedemann; Stefan Schwaiger; Adrian Türkcan; Christian Ploner; Alexander Trockenbacher; Klaus Aumayr; Nikolaos Bonaros; Günther Laufer; Hermann Stuppner; Gerold Untergasser; David Bernhard

doi:10.1371/journal.pone.0058342

5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo

Barbara Messner
, Johann Kern
, Dominik Wiedemann
, Stefan Schwaiger
, Adrian Türkcan
, Christian Ploner
, Alexander Trockenbacher
, Klaus Aumayr
, Nikolaos Bonaros
, Günther Laufer
, Hermann Stuppner
, Gerold Untergasser
, David Bernhard

Research output: Journal article (peer-reviewed) › Journal article

13 Citations (Scopus)

Abstract

BACKGROUND: Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.

METHODS AND RESULTS: 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).

CONCLUSION: The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.

Original language	English
Article number	e58342
Pages (from-to)	e58342
Journal	PLoS ONE
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0058342
Publication status	Published - 12 Mar 2013
Externally published	Yes

Keywords

Animals
Arterioles/enzymology
Asteraceae/chemistry
Chick Embryo
Coronary Circulation/drug effects
Coronary Vessels/enzymology
Cytochrome P-450 Enzyme System/metabolism
Disease Models, Animal
Human Umbilical Vein Endothelial Cells
Humans
Lignans/chemistry
Male
Myocardial Infarction/drug therapy
Myocardium/enzymology
Neovascularization, Physiologic/drug effects
Rats
Rats, Wistar
Retinoic Acid 4-Hydroxylase
Ventricular Function, Left/drug effects

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0058342

Cite this

Messner, B., Kern, J., Wiedemann, D., Schwaiger, S., Türkcan, A., Ploner, C., Trockenbacher, A., Aumayr, K., Bonaros, N., Laufer, G., Stuppner, H., Untergasser, G., & Bernhard, D. (2013). 5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo. PLoS ONE, 8(3), e58342. Article e58342. https://doi.org/10.1371/journal.pone.0058342

@article{ab850c77d8b54f2f85a2f9ff12d02441,

title = "5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo",

abstract = "BACKGROUND: Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.METHODS AND RESULTS: 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21\% 28 days after MI).CONCLUSION: The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.",

keywords = "Animals, Arterioles/enzymology, Asteraceae/chemistry, Chick Embryo, Coronary Circulation/drug effects, Coronary Vessels/enzymology, Cytochrome P-450 Enzyme System/metabolism, Disease Models, Animal, Human Umbilical Vein Endothelial Cells, Humans, Lignans/chemistry, Male, Myocardial Infarction/drug therapy, Myocardium/enzymology, Neovascularization, Physiologic/drug effects, Rats, Rats, Wistar, Retinoic Acid 4-Hydroxylase, Ventricular Function, Left/drug effects",

author = "Barbara Messner and Johann Kern and Dominik Wiedemann and Stefan Schwaiger and Adrian T{\"u}rkcan and Christian Ploner and Alexander Trockenbacher and Klaus Aumayr and Nikolaos Bonaros and G{\"u}nther Laufer and Hermann Stuppner and Gerold Untergasser and David Bernhard",

year = "2013",

month = mar,

day = "12",

doi = "10.1371/journal.pone.0058342",

language = "English",

volume = "8",

pages = "e58342",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3",

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Messner, B, Kern, J, Wiedemann, D, Schwaiger, S, Türkcan, A, Ploner, C, Trockenbacher, A, Aumayr, K, Bonaros, N, Laufer, G, Stuppner, H, Untergasser, G & Bernhard, D 2013, '5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo', PLoS ONE, vol. 8, no. 3, e58342, pp. e58342. https://doi.org/10.1371/journal.pone.0058342

TY - JOUR

T1 - 5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo

AU - Messner, Barbara

AU - Kern, Johann

AU - Wiedemann, Dominik

AU - Schwaiger, Stefan

AU - Türkcan, Adrian

AU - Ploner, Christian

AU - Trockenbacher, Alexander

AU - Aumayr, Klaus

AU - Bonaros, Nikolaos

AU - Laufer, Günther

AU - Stuppner, Hermann

AU - Untergasser, Gerold

AU - Bernhard, David

PY - 2013/3/12

Y1 - 2013/3/12

N2 - BACKGROUND: Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.METHODS AND RESULTS: 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).CONCLUSION: The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.

AB - BACKGROUND: Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.METHODS AND RESULTS: 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).CONCLUSION: The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.

KW - Animals

KW - Arterioles/enzymology

KW - Asteraceae/chemistry

KW - Chick Embryo

KW - Coronary Circulation/drug effects

KW - Coronary Vessels/enzymology

KW - Cytochrome P-450 Enzyme System/metabolism

KW - Disease Models, Animal

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Lignans/chemistry

KW - Male

KW - Myocardial Infarction/drug therapy

KW - Myocardium/enzymology

KW - Neovascularization, Physiologic/drug effects

KW - Rats

KW - Rats, Wistar

KW - Retinoic Acid 4-Hydroxylase

KW - Ventricular Function, Left/drug effects

UR - https://www.scopus.com/pages/publications/84874873449

U2 - 10.1371/journal.pone.0058342

DO - 10.1371/journal.pone.0058342

M3 - Journal article

C2 - 23554885

SN - 1932-6203

VL - 8

SP - e58342

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e58342

ER -

5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo

Abstract

Keywords

UN SDGs

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