Abstract 17878: Galectin-2 Expression is Dependent on the rs7291467 Single Nucleotide Polymorphism and Inhibits Collateral Artery Growth
Background In patients with obstructive coronary artery disease, the remodeling of small arterioles into large collateral arteries is an important natural mechanism to preserve myocardial tissue perfusion. This process is critically dependent on mononuclear cells, especially monocytes. In the present study, we investigated the gene expression profiles of monocytes of 50 patients with a chronic total coronary occlusion, to find targets that relate to the capacity of the collateral circulation.
Methods and Results In all 50 patients, the coronary collateral flow index (CFI) was invasively measured using intracoronary guidewire-based pressure sensors. From each patient, RNA was isolates from unstimulated peripheral blood monocytes, monocytes stimulated by lipopolysaccharide, or from monocytes after differentiation into macrophages. Whole genome transcriptome analysis revealed increased mRNA expression of galectin-2 in all three monocytic cell types of the patients with a low capacity of the collateral circulation. Interestingly, patients with a genetic substitution (3279C◊T) in intron 1 of the galectin-2 gene (rs7291467) displayed decreased mRNA levels of galectin−2. Likewise, these patients had a high capacity of the collateral circulation. Galectin-2 was expressed on the surface of monocytes, and in vitro stimulation of monocytes with exogenous galectin-2 changed their cytokine expression profile in a pro-inflammatory direction. In a murine hindlimb model, the administration of galectin-2 markedly impaired collateral artery growth (see Figure), without apparent systemic effects on the immune system.
Conlusion Collectively, these results identify galectin-2 as an inhibitor of collateral artery growth, most likely due to local modulation of the monocytic phenotype. Blockage of galectin-2 may constitute a novel therapeutic strategy for the stimulation of collateral artery growth in patients with coronary artery disease.
- © 2010 by American Heart Association, Inc.