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Kidney Week

Abstract: PO0365

Elastin-Like Polypeptide Vascular Endothelial Growth Factor (ELP-VEGF) Improves Renal Function and Decreases Inflammation Following Ischemia-Reperfusion Injury in Mice

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Ullah, Md Mahbub, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Mehrotra, Purvi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Chade, Alejandro R., The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Bidwell, Gene L., The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Acute Kidney Injury (AKI) represents a significant clinical concern and significant risk factor for the development of chronic kidney disease (CKD). AKI is associated with impaired renal function, increased inflammation and microvascular congestion, damage and loss. A fusion protein between the elastin-like polypeptide biopolymer and human VEGF-A121 (ELP-VEGF) efficiently targets the renal vasculature and promotes vascular protection and angiogenesis, while potentially altering inflammatory processes. However, it is unknown if ELP-VEGF administration following ischemia-reperfusion mitigates injury, facilitates vascular protection and hastens repair.

Methods

Male C57BL/6 mice were subjected to unilateral ischemia (I/R) for 25 minutes. Post-ischemic animals were treated daily with either vehicle or ELP-VEGF (10ug/kg bw; i.p) at reperfusion, and every 24 hours for 7 days. Serum creatine (sCre) and BUN were collected 24 hours and 7 days following ischemia to assess renal function. At day 7, kidneys were harvested for analysis of infiltration of inflammatory cells by FACS and measurement of peritubular capillary density by immunofluorescent staining.

Results

Increases in BUN following unilateral I/R were significantly attenuated in the ELP-VEGF treated group compared with vehicle at both 24 hours (66% vs. 15%) and 7 days (49% vs. 19%) following ischemia (p<0.05). I/R significantly reduced the number of CD31+ endothelial cells in the injured kidney of the vehicle-treated mice compared with sham (p<0.05), and ELP-VEGF attenuated that reduction. ELP-VEGF also attenuated the pro-inflammatory response following I/R, with significant reductions in total number of infiltrating mononuclear cells (p<0.05). In ELP-VEGF treated mice, there was a significant reduction in Th17 cells (CD4+IL17+; 408236 vs. 182277 cells/g kidney: CD8+IL17+; 484483 vs. 99391 cells/g kidney), DC/Macrophages (12404078 vs 4764147 cells/g kidney) and B cells (16201335 vs. 7641714 cells/g kidney) compared with vehicle treated rats (p<0.05).

Conclusion

ELP-VEGF represents a novel reno-protective therapeutic compound related to its anti-inflammatory and renovascular protective effects.

Funding

  • NIDDK Support