Abstract 3874: Galectin-3 Enhances Post Ischemic Angiogenesis Via Modulation Of Integrin And Akt Pathways

Introduction: As restoration of blood flow is critical for improved functional recovery following ischemic stroke, enhancing cerebral angiogenesis might be immensely helpful. Galectin-3 (gal-3) is a β-galactoside-binding lectin that plays key roles in inflammation, survival, and angiogenesis. Methods: We used transient middle cerebral artery occlusion (MCAO), oxygen-glucose deprivation (OGD) model, western blot analysis, RT-PCR, Immunofluorescence staining. Results: We currently report that intra-cerebroventricular infusion of recombinant gal-3 in rats subjected to transient MCAO increases the post-ischemic functional recovery. We further show that gal-3 mRNA and protein expression is up-regulated in vitro when activated microglial BV2 cells were subjected to either oxygen-glucose deprivation (OGD) or LPS (lipo-polysaccharide) stimulation. Immunofluorescence staining showed increased cytoplasmic gal-3 that is known to have pro-survival function. This increase in gal-3 is associated with increased number of pro-angiogenic structures in a 3D human vein umbilical cord endothelial (HUVEC) and microglia co-culture model. The pro-angiogenic effect of gal-3 was suppressed by treatment with gal-3 siRNA indicating the specific role of gal-3 in promoting angiogenesis. Exogenous gal-3 treatment further augmented the angiogenic potential of BV2 microglia cells. In addition, gal-3 increased survival of microglial BV2 cells, HUVEC, and neuro-progenitor cells. Gal-3 levels were also directly correlated with increased levels of Integrin-linked kinase 1(ILK1), pro-survival factor AKT and their down stream effector pro-angiogenic factors bFGF and MMP2. Conclusion: Taken together, our studies emphasize the importance of gal-3 in enhancing angiogenesis that is critical for neuron survival and neurogenesis in the post-stroke brain.