Intra‐Renal Delivery of Progenitor Cells Improves Systemic Inflammation, Oxidative Stress, and Myocardial Microvascular Function in Experimental Renovascular Disease

Abstract

Renovascular disease (RVD) and hypertension (HT) are cardiovascular risk factors, but if recovery of renal function can reverse cardiac dysfunction remained unclear.We hypothesized that improved stenotic kidney function would rescue myocardial microvascular (MMV) function in renovascular HT by reducing oxidative stress and inflammation.Single‐kidney hemodynamics and function and MMV permeability were assessed in pigs in vivo using CT after 6 weeks of RVD. Autologous endothelial progenitor cells (EPC) were then infused intra‐renally, and studies repeated 4 weeks later (RVD+EPC, n=7). Normal and untreated RVD (n=7 each) served as controls.Blood pressure was similarly increased in RVD and RVD+EPC pigs. Compared to normal, RVD showed elevated systemic TNF‐alpha (142.3± 3.7 vs 43.3 ± 3.5 pg/ml, p<0.001) and oxidized‐LDL, blunted glomerular filtration rate (47.9±10.1 vs 70.8 ± 4.3 ml/min, p<0.05), decreased MMV volume fraction, increased MMV permeability, and myocardial fibrosis.EPC were rarely observed in myocardium. However, RVD+EPC showed a decrease in TNF‐alpha (90.5± 2.9, p<0.01 vs RVD) and oxidized‐LDL, implying decreased inflammation and oxidative stress. Furthermore, not only renal, but also MMV function were significantly improved in RVD+EPC.In conclusion, selective improvement in renal function reduces oxidative stress and inflammation and preserves remote MMV function, underscoring functionally important cardiorenal crosstalk.