title: Vascular therapy for radiation cystitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Urology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Soler
authors.forename: Alberto
authors.initials: A
authors.lastname: Vianello
authors.forename: Claudius
authors.initials: C
authors.lastname: Füllhase
authors.forename: Zhan
authors.initials: Z
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Shay
authors.initials: S
authors.lastname: Soker
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: James
authors.initials: J
authors.lastname: Koudywilliam
mesh_terms: D000283:Administration, Intravesical; D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003556:Cystitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D001743:Urinary Bladder / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D014841:von Willebrand Factor; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2