Vascular endothelial growth factor accelerates renal recovery in experimental thrombotic microangiopathy

Background. Renal microvascular injury characterizes thrombotic microangiop athy (TMA). The possibility that angiogenic growth factors may accelerate r ecovery in TMA has not been studied. Methods. TMA was induced in rats by the selective right renal artery perfus ion of antiglomerular endothelial cell IgG (30 mg/kg). Twenty-four hours la ter, rats received vascular endothelial growth factor (VEGF(121), 100 mug/k g/day) or vehicle (control) daily until day 14. To evaluate renal function, the unperfused left kidney was removed at day 14, and rats were sacrificed at day 17. Results. The induction of TMA was associated with loss of glomerular and pe ritubular capillary endothelial cells and decreased arteriolar density at d ay 1. Some spontaneous capillary recovery was present by day 17; however, r epair was incomplete, and severe tubulointerstitial damage occurred. The la ck of complete microvascular recovery was associated with reduced VEGF immu nostaining in the outer medulla. VEGF-treated rats had more glomeruli with intact endothelium, less glomerular ischemia (collapsed glomeruli), and gre ater peritubular capillary density with less peritubular capillary loss. Th is was associated with less tubulointerstitial fibrosis, less cortical atro phy, and improved renal function. Conclusions. VEGF accelerates renal recovery in this experimental model of TMA. These studies suggest that angiogenic growth factors may provide a new therapeutic strategy for diseases associated with endothelial cell injury.