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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.
- Source :
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European heart journal [Eur Heart J] 2012 May; Vol. 33 (9), pp. 1076-84. Date of Electronic Publication: 2011 Aug 10. - Publication Year :
- 2012
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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.
- Subjects :
- Aged
Animals
Cardiovascular Agents pharmacology
Collateral Circulation drug effects
Coronary Occlusion metabolism
Coronary Occlusion physiopathology
Female
Galectin 2 genetics
Galectin 2 pharmacology
Hindlimb
Humans
Interleukin-4 pharmacology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Monocytes drug effects
RNA, Messenger metabolism
Collateral Circulation genetics
Coronary Occlusion genetics
Galectin 2 metabolism
Polymorphism, Genetic genetics
Subjects
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