Abstract 5757: RAGE in Bone Marrow Derived Cells Blunts Restoration of Blood Flow in Mice Subjected to Femoral Artery Ligation

Abstract

Receptor for Advanced Glycation Endproducts (RAGE) plays central roles in the injury response to global hypoxia and ischemia/reperfusion (I/R) injury. Our previous data revealed that diabetic (D) and non-diabetic (ND) homozygous RAGE null mice subjected to hind limb ischemia displayed improvement in angiogenesis and restoration of blood flow. Here, we tested the hypothesis that endogenous RAGE expression in bone marrow (BM)-derived cells may contribute to impaired angiogenesis and blunted restoration of blood flow after femoral artery (FA) ligation. Wild type (WT) mice were rendered diabetic (D) with streptozotocin (stz); non-diabetic (ND) cohorts were treated with buffer alone. N D or D WT mice were used as recipient mice in BM transplantation. Rosa +/− transgenic mice containing a lacZ reporter gene were used as an indicator of transplantation of RAGE +/+ or RAGE −/− BM, therefore, the chimerical mice containing RAGE +/+ /Rosa +/− or RAGE −/− /Rosa +/− were generated as donor strains for BM transplantation. Immunostaining with anti- β -galactosidase IgG demonstrated that BM transplantation was successful from donors to recipients by localization of the expression of LacZ gene in the muscle tissues. FA ligation was performed on 13-week old ND or D WT recipient mice. Both ND and D WT recipient mice with transplantation of RAGE −/− /Rosa +/− BM displayed significantly improved blood flow ratios (injured/contralateral leg) by laser Doppler analysis on day 28 after FA ligation compared to ND or D WT recipient mice with transplantation of RAGE +/+ /Rosa +/− BM (Table ). Our data suggested that RAGE expression in the bone marrow contributes to impairment in blood flow recovery after acute arterial injury, irrespective of the state of glycemia. Table. Doppler data of Blood Flow Ratios (BRF, %)