P0144LOW-ENERGY SHOCKWAVE TREATMENT PROMOTES ENDOTHELIAL PROGENITOR CELL HOMING TO THE STENOTIC PIG KIDNEY

Abstract

Abstract Background and Aims Endothelial progenitor cells (EPCs) patrol the circulation and contribute to endothelial cell regeneration and tissue revascularization. Atherosclerotic renal artery stenosis (ARAS) induces microvascular loss in the stenotic kidney. A regimen of low–energy shockwave therapy (SW) induces angiogenesis and reduces chronic ischemia, but the mechanism remains unclear. This study tested the hypothesis that SW increases EPCs homing to the stenotic kidney and increases renal capillary regeneration in a unilateral ARAS swine model. Method Domestic pigs were randomized to normal control or unilateral ARAS (induced by a local irritant coil in the renal artery and a high-fat diet). ARAS pigs were treated with low-energy SW (0.1 mJ/mm2) or sham (n=6 each group), bi-weekly for 3 consecutive weeks, starting after 3 weeks of ARAS. Blood samples for EPCs (CD34+ and KDR+ by flow cytometry) and the homing factor SDF-1 were collected 4 weeks after completion of SW treatment from the inferior vena cava (IVC) and the stenotic kidney (STK) vein and artery. Urine was collected from the urinary bladder. Kidneys were studied ex vivo for morphology and expression of an endothelial cell marker (CD31) and the pro- angiogenic growth factor angiopoietin (Ang)-1. Results In ARAS, tubulointerstitial fibrosis, tubular score, urinary protein, serum creatinine and mean arterial pressure were significantly increased and capillary count (Fig. 1A) decreased (P<0.05 vs. control), but all markedly improved in ARAS+SW (P<0.05 vs. ARAS). EPC number was decreased in the IVC and renal artery of ARAS pigs (Fig. 1B), but improved in ARAS+SW. SDF-1 levels in the IVC, STK vein and artery, and Ang-1 expression in the kidney of ARAS+SW, were all increased (P<0.05 vs. ARAS). Conclusion Low-energy shockwave improves ischemic kidney capillary density, which is associated with and may be at least in part mediated by promoting EPC mobilization and homing to the stenotic kidney.