Tissue injury triggers reparative processes that often involve endothelial progenitor cells (EPCs) recruitment. We hypothesized that atherosclerotic
renal artery stenosis (ARAS) activates homing signals that would be detectable in both the kidney and EPCs, and attenuated on renal repair using selective cell-based
therapy. Pigs were treated with intrarenal autologous
EPC after 6 weeks of ARAS. Four weeks later, expression of homing-related signals in
EPC and
kidney, single kidney function, microvascular (MV) density, and morphology were compared with untreated ARAS and normal control pigs (n = 7 each). Compared with normal
EPC,
EPC from ARAS pigs showed increased stromal cell-derived factor (SDF)-1,
angiopoietin-1, Tie-2, and c-kit expression, but downregulation of
erythropoietin (EPO) and its receptor. The ARAS kidney released the
c-kit-ligand stem cell factor,
uric acid, and EPO, and upregulated
integrin beta2, suggesting activation of corresponding homing signaling. However,
angiopoietin-1 and SDF-1/CXCR4 were not elevated. Administration of
EPC into the stenotic kidney restored angiogenic activity, improved MV density, renal hemodynamics and function, decreased
fibrosis and oxidative stress, and attenuated endogenous injury signals. The ARAS kidney releases specific homing signals corresponding to cognate receptors expressed by
EPC.
EPC show plasticity for organ-specific recruitment strategies, which are upregulated in early
atherosclerosis.
EPC are renoprotective as they attenuated renal dysfunction and damage in chronic ARAS, and consequently decreased the injury signals. Importantly, manipulation of homing signals may potentially allow therapeutic opportunities to increase endogenous
EPC recruitment.