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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Messner
authors.forename: Johann
authors.initials: J
authors.lastname: Kern
authors.forename: Dominik
authors.initials: D
authors.lastname: Wiedemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Adrian
authors.initials: A
authors.lastname: Türkcan
authors.forename: Christian
authors.initials: C
authors.lastname: Ploner
authors.forename: Alexander
authors.initials: A
authors.lastname: Trockenbacher
authors.forename: Klaus
authors.initials: K
authors.lastname: Aumayr
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Bonaros
authors.forename: Günther
authors.initials: G
authors.lastname: Laufer
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Gerold
authors.initials: G
authors.lastname: Untergasser
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D000818:Animals; D001160:Arterioles / Q000201:enzymology / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D019659:Asteraceae / Q000737:chemistry*; D002642:Chick Embryo; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000072516:Retinoic Acid 4-Hydroxylase; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D017705:Lignans; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; C000607082:Cyp26b1 protein, rat; D000072516:Retinoic Acid 4-Hydroxylase
references.citation: Circulation. 2000 Jun 27;101(25):2981-8
references.pmid: 10869273
references.citation: Mol Ther. 2008 May;16(5):972-978
references.pmid: 28178491
references.citation: Biostatistics. 2003 Apr;4(2):249-64
references.pmid: 12925520
references.citation: Cancer Chemother Pharmacol. 2011 Sep;68(3):619-29
references.pmid: 21120482
references.citation: Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):833-8
references.pmid: 16439709
references.citation: Circulation. 2002 Oct 22;106(17):2257-62
references.pmid: 12390957
references.citation: Atherosclerosis. 2008 Dec;201(2):298-305
references.pmid: 18405900
references.citation: Planta Med. 2004 Oct;70(10):978-85
references.pmid: 15490327
references.citation: Cardiovasc Res. 2009 Jun 1;82(3):542-9
references.pmid: 19228707
references.citation: J Neurobiol. 2006 Jun;66(7):606-30
references.pmid: 16688755
references.citation: Acta Biochim Biophys Sin (Shanghai). 2008 Aug;40(8):681-92
references.pmid: 18685784
references.citation: Circulation. 1998 Dec 22-29;98(25):2800-4
references.pmid: 9860779
references.citation: FASEB J. 2003 Apr;17(6):770-2
references.pmid: 12586744
references.citation: Circ Res. 2009 Nov 6;105(10):994-1002
references.pmid: 19797703
references.citation: Circulation. 2008 Jan 29;117(4):e25-146
references.pmid: 18086926
references.citation: Nat Med. 2001 Apr;7(4):430-6
references.pmid: 11283669
references.citation: Annu Rev Physiol. 1991;53:217-39
references.pmid: 1710435
references.citation: Int J Cardiol. 2011 Dec 15;153(3):239-40
references.pmid: 22108502
references.citation: Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1392-8
references.pmid: 19556524
references.citation: Atherosclerosis. 2011 Nov;219(1):109-15
references.pmid: 21820657
references.citation: Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1733-40
references.pmid: 20595649
references.citation: Circulation. 1992 Mar;85(3):1197-204
references.pmid: 1371432
references.citation: Science. 1989 Dec 8;246(4935):1306-9
references.pmid: 2479986
references.citation: J Cell Mol Med. 2006 Jul-Sep;10(3):588-612
references.pmid: 16989723
references.citation: J Cell Sci. 1999 Oct;112 ( Pt 19):3249-58
references.pmid: 10504330
references.citation: Planta Med. 2004 Jun;70(6):502-8
references.pmid: 15241889
references.citation: Circulation. 2007 Feb 6;115(5):e69-171
references.pmid: 17194875
references.citation: Am J Pathol. 2005 Feb;166(2):615-24
references.pmid: 15681843