Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

Perit Dial Int. 2022 Jan;42(1):25-38. doi: 10.1177/08968608211004683. Epub 2021 Apr 7.

Abstract

Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal diseases, which is limited by peritoneal neoangiogenesis leading to ultrafiltration failure (UFF). Vascular endothelial growth factor (VEGF) and its receptors are key angiogenic factors involved in almost every step of peritoneal neoangiogenesis. Impaired mesothelial cells are the major sources of VEGF in the peritoneum. The expression of VEGF will be up-regulated in specific pathological conditions in PD patients, such as with non-biocompatible peritoneal dialysate, uremia and inflammation, and so on. Other working cells (i.e. vascular endothelial cells, macrophages and adipocytes) can also stimulate the secretion of VEGF. Meanwhile, hypoxia and activation of complement system further aggravate peritoneal injury and contribute to neoangiogenesis. There are several signalling pathways participating in VEGF-mediated peritoneal neoangiogenesis including tumour growth factor-β, Wnt/β-catenin, Notch and interleukin-6/signal transducer and activator of transcription 3. Moreover, VEGF is highly expressed in dialysate effluent of long-term PD patients and is associated with peritoneal transport function, which supports its role in the alteration of peritoneal structure and function. In this review, we systematically summarize the angiogenic effect of VEGF and evaluate it as a potential target for the prevention of peritoneal neoangiogenesis and UFF. Preservation of the peritoneal membrane using targeted therapy of VEGF-mediated peritoneal neoangiogenesis may increase the longevity of the PD modality for those who require life-long dialysis.

Keywords: Peritoneal dialysis; peritoneal neoangiogenesis; targeted therapy; ultrafiltration failure; vascular endothelial growth factor.

Publication types

  • Review

MeSH terms

  • Dialysis Solutions / chemistry
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Male
  • Neovascularization, Pathologic / metabolism
  • Peritoneal Dialysis* / adverse effects
  • Peritoneum / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factors / metabolism
  • Vascular Endothelial Growth Factors / pharmacology

Substances

  • Dialysis Solutions
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors