title: Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis.
abstract: OBJECTIVE
  In patients with obstructive coronary artery disease (CAD), the growth of collateral arteries, i.e. arteriogenesis, can preserve myocardial tissue perfusion and function. Monocytes modulate this process, supplying locally the necessary growth factors and degrading enzymes. Knowledge on factors involved in human arteriogenesis is scarce. Thus, the aim of the present study is to identify targets in monocytes that are critical for arteriogenesis in patients with CAD.
  
  
  RESULTS
  A total of 50 patients with a chronic total coronary occlusion were dichotomized according to their collateral flow index. From each patient, RNA was isolated from unstimulated peripheral blood monocytes, monocytes stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4, and from macrophages. Increased mRNA expression of galectin-2 was found in three out of four monocytic cell types of patients with a low capacity of the collateral circulation (P= 0.03 for unstimulated monocytes; P= 0.02 for LPS-stimulated monocytes; P= 0.20 for IL-4-stimulated monocytes; P= 0.02 for macrophages). Additionally, galectin-2 mRNA expression was significantly associated with the rs7291467 polymorphism in LGALS2 encoding galectin-2 in all four monocytic cell types. Patient with the rs7291467 CC genotype displayed highest galectin-2 expression, and also tended to have a lower arteriogenic response. To evaluate the effect of galectin-2 on arteriogenesis in vivo, we used a murine hindlimb model. Treatment with galectin-2 markedly impaired the perfusion restoration at Day 7.
  
  
  CONCLUSIONS
  Collectively, these results identify galectin-2 as a novel inhibitor of arteriogenesis. Modulation of galectin-2 may constitute a new therapeutic strategy for the stimulation of arteriogenesis in patients with CAD.
authors.affiliation: Department of Cardiology,  Academic Medical Centre, University of Amsterdam, Amsterdam,  The Netherlands.
authors.forename: Anja M
authors.initials: AM
authors.lastname: van der Laan
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Schirmer
authors.forename: Margreet R
authors.initials: MR
authors.lastname: de Vries
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Koning
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Volger
authors.forename: Joost O
authors.initials: JO
authors.lastname: Fledderus
authors.forename: Antonius J N M
authors.initials: AJ
authors.lastname: Bastiaansen
authors.forename: Maurits R
authors.initials: MR
authors.lastname: Hollander
authors.forename: Josefien M
authors.initials: JM
authors.lastname: Baggen
authors.forename: Karel T
authors.initials: KT
authors.lastname: Koch
authors.forename: Jan
authors.initials: J
authors.lastname: Baan
authors.forename: José P
authors.initials: JP
authors.lastname: Henriques
authors.forename: René J
authors.initials: RJ
authors.lastname: van der Schaaf
authors.forename: Marije M
authors.initials: MM
authors.lastname: Vis
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
authors.forename: Tineke C
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: Paul H
authors.initials: PH
authors.lastname: Quax
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Horrevoets
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
mesh_terms: D000368:Aged; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D003097:Collateral Circulation / Q000187:drug effects / Q000235:genetics*; D054059:Coronary Occlusion / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D037501:Galectin 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006614:Hindlimb; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D037501:Galectin 2; D012333:RNA, Messenger; D015847:Interleukin-4