Abstract 982: RAGE Modulates Vascular Remodeling: Critical Contribution of BM Progenitors and Local Cells of the Vessel Wall
Receptor for advanced glycation end products (RAGE) is importantly involved in vascular remodeling consequent to acute vascular injury. Our previous findings demonstrated key roles for the RAGE-axis in the homing of the bone marrow (BM) c-kit+,Sca-1+,Lin− stem cells to the site of vascular injury. To gain a better understanding of BM/local contribution of the RAGE-axis we have performed studies in chimeric mice reconstituted with BM-cells expressing Lac-Z. Chimeric mice were generated expressing either RAGE null (RKO) or wild-type (WT) BM into RKO or WT host. Importantly, when WT BM reconstituted WT mice, consequent to vascular injury, most of the SMA Lac-Z positive cells in the groups I and III expressed RAGE on their surface (mean 66±9.3%). I Table⇓ illustrates that RKO BM critically modulated both I/M ratio and the % BM-derived cells in neointima. Further, these data indicate that there is a partial contribution of local RAGE-expressing cells to neointima production (gp. III vs gp. I). To further test the underlying mechanisms, we employed soluble RAGE, the extracellular ligand binding decoy of RAGE. Consequent to arterial injury, an ≈3-fold dcrease in BM MMP-9 activity was noted in the sRAGE- vs. vehicle-treated mice; p<0.05. Taken together, these data critically link both BM and local vessel wall RAGE-expressing cells to vascular remodeling consequent to acute arterial injury.