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. 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. 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.
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. 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. 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.
Authors: Maarten A Lijkwan; Alwine A Hellingman; Ernst J Bos; Koen E A van der Bogt; Mei Huang; Nigel G Kooreman; Margreet R de Vries; Hendrika A B Peters; Robert C Robbins; Jaap F Hamming; Paul H A Quax; Joseph C Wu Journal: Hum Gene Ther Date: 2014-01-07 Impact factor: 5.695
Authors: C M Werner; S H Schirmer; C Gensch; V Pavlickova; J Pöss; M B Wright; M Böhm; U Laufs Journal: Br J Pharmacol Date: 2014-05 Impact factor: 8.739
Authors: Joan Duran; Pilar Sánchez Olavarría; Marina Mola; Víctor Götzens; Julio Carballo; Eva Martín Pelegrina; Màrius Petit; Omar Abdul-Jawad; Imanol Otaegui; Bruno García del Blanco; David García-Dorado; Josep Reig; Alex Cordero; Josep Maria de Anta Journal: BMC Cardiovasc Disord Date: 2015-05-12 Impact factor: 2.298
Authors: Cansu Yıldırım; Daphne Y S Vogel; Maurits R Hollander; Josefien M Baggen; Ruud D Fontijn; Sylvia Nieuwenhuis; Anouk Haverkamp; Margreet R de Vries; Paul H A Quax; Juan J Garcia-Vallejo; Anja M van der Laan; Christine D Dijkstra; Tineke C T M van der Pouw Kraan; Niels van Royen; Anton J G Horrevoets Journal: PLoS One Date: 2015-04-17 Impact factor: 3.240