Vascular therapy for radiation cystitis

Neurourol Urodyn. 2011 Mar;30(3):428-34. doi: 10.1002/nau.21002. Epub 2010 Oct 29.


Purpose: The underlying pathology of radiation cystitis is cellular and vascular damage followed by increased fibrosis and inflammation. This study was to determine if neovascular-promoting therapy could reduce the pathological changes in the bladder wall associated with pelvic irradiation.

Methods: Adult female Lewis inbred rats were irradiated with a single dose of 20 Gy directed at their bladder. Four weeks later, 30 rats were divided equally into one of three treatment groups for bladder wall injection of: (1) PBS (Control); (2) PBS containing 50 ng vascular endothelial growth factor (VEGF (165)); or (3) PBS containing 1 × 10(6) rat endothelial cells (EC). Age-matched non-irradiated rats (n = 10) served as untreated controls. At either 1.5 or 3 months following radiation, bladders were analyzed for collagen deposition using Masson's Trichrome staining of collagen and muscle and vascularization using Von Willebrand factor staining of ECs. Quantitative-PCR was used to examine markers of angiogenesis, hypoxia, and fibrosis.

Results: The collagen/muscle ratio was doubled in the control group 3 months post-irradiation (P < 0.05 vs. non-irradiated bladders). Both ECs and VEGF inhibited increases in collagen content (P < 0.05 vs. control). Similarly, irradiation reduced bladder wall vessel counts compared to non-irradiated controls (P < 0.05) and both ECs and VEGF maintained vessel counts similar to that of non-irradiated controls (P < 0.05). PCR analysis showed a higher expression of neovascular markers (CD31, KDR) in the EC and VEGF groups compared to non-irradiated controls (P < 0.05).

Conclusions: Angiogenesis therapy may be useful in the prevention and/or treatment of the underlying pathology of radiation cystitis.

MeSH terms

  • Administration, Intravesical
  • Analysis of Variance
  • Angiogenesis Inducing Agents / administration & dosage*
  • Animals
  • Collagen / metabolism
  • Cystitis / genetics
  • Cystitis / metabolism
  • Cystitis / pathology
  • Cystitis / physiopathology
  • Cystitis / therapy*
  • Endothelial Cells / metabolism
  • Endothelial Cells / transplantation*
  • Female
  • Fibrosis
  • Gene Expression Regulation
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Radiation Injuries, Experimental / genetics
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / physiopathology
  • Radiation Injuries, Experimental / therapy*
  • Rats
  • Rats, Inbred Lew
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Urinary Bladder / blood supply*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • von Willebrand Factor / metabolism


  • Angiogenesis Inducing Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • von Willebrand Factor
  • Collagen
  • Vascular Endothelial Growth Factor Receptor-2