Abstract TP221: Protective Effects Of Galectin-3 On Endothelial Progenitor Cells Under Ischemic Conditions

Abstract

Stroke remains the major cause of long term functional deficits and death with limited treatment options. Ischemic stroke leads to endothelial dysfunction, blood brain barrier disruption, poor angiogenesis, inflammation, and neuronal cell death. Stem/Progenitor cells including mesenchymal, neural, and endothelial progenitor cells (EPC) can enhance tissue regeneration and repair. However, the beneficial effects of progenitor cells have been modest presumably due to their poor recruitment and survival in an ischemic microenvironment. Galectin-3 (Gal3), a β-galactoside-binding protein controls cell proliferation, survival, angiogenesis, and migration/recruitment. We have shown that the expression of Gal3 is significantly up-regulated in ischemic rat brain, and that blocking of Gal3 decreases the cerebral blood vessel density. We recently demonstrated that Gal3 reduces cerebral infarction and enhances recovery of motor/sensory functions in an animal stroke model. In this study we examined the effects of Gal3 on bone marrow derived EPC. EPCs were characterized by the uptake of acetylated LDL and expression of CD34 and VEGFR2/KDR. We further demonstrate that Gal3 enhances the proliferation, angiogenesis, migration, and survival of bone marrow derived EPCs in an in vitro ischemic conditions following oxygen glucose deprivation. Gal3 effects were associated with up-regulation of chemoattractant SDF1 and VEGF, further emphasizing the role of Gal3 in stem/progenitor function. Overall, these results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways in progenitor cells.