Back to Search Start Over

Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis.

Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis.

Authors :
van der Laan AM
Schirmer SH
de Vries MR
Koning JJ
Volger OL
Fledderus JO
Bastiaansen AJ
Hollander MR
Baggen JM
Koch KT
Baan J Jr
Henriques JP
van der Schaaf RJ
Vis MM
Mebius RE
van der Pouw Kraan TC
Quax PH
Piek JJ
Horrevoets AJ
van Royen N
Source :
European heart journal [Eur Heart J] 2012 May; Vol. 33 (9), pp. 1076-84. Date of Electronic Publication: 2011 Aug 10.
Publication Year :
2012

Abstract

Aims: 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.<br />Methods and 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.<br />Conclusion: 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.

Details

Language :
English
ISSN :
1522-9645
Volume :
33
Issue :
9
Database :
MEDLINE
Journal :
European heart journal
Publication Type :
Academic Journal
Accession number :
21831908
Full Text :
https://doi.org/10.1093/eurheartj/ehr220