title: Cyclooxygenase-2 and vascular endothelial growth factor expressions are involved in ultrafiltration failure.
abstract: BACKGROUND
  Long-term peritoneal dialysis (PD) is associated with ultrafiltration failure (UFF). The aim of the study was to investigate changes in cyclooxygenase-2 (COX-2), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor C (VEGF-C) expressions in a rat model of UFF induced by PD solution.
  
  
  METHODS
  Sprague-Dawley rats were divided into six groups (n = 8/group): normal untreated control group, sham operation group, uremic group (nephrectomy without PD), uremic 2-wk PD group (PD solution for 2 wk), uremic 4-wk PD group (PD solution for 4 wk), and uremic 4-wk PD + celecoxib group (PD solution plus COX-2 inhibitor celecoxib 20 mg/kg for 4 wk). Peritoneal function was determined by peritoneal equilibration test. Peritoneal morphology was determined by hematoxylin and eosin and Masson staining. Microvessel and lymphatic microvessel formation was determined by immunohistochemistry. COX-2, VEGF-A, and VEGF-C expressions were determined by real-time polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  Uremic rat model was successfully established. PD-induced peritoneal morphologic changes associated with UFF, characterized by inflammation, edema, and collagen accumulation. PD solution increased the density of microvessels marked by CD31 (microvessel density) and lymphatic microvessels marked by LYVE-1 (lymphatic vessel density) in peritoneum. COX-2, VEGF-A, and VEGF-C expression levels in the uremic 4-wk PD group were higher than those in the uremic group (all P < 0.05). All these changes were partially reversed by celecoxib. VEGF-A and VEGF-C protein expressions were positively correlated with microvessel density and lymphatic vessel density formation.
  
  
  CONCLUSIONS
  COX-2 could increase VEGF-A and VEGF-C expressions in peritoneal tissue, resulting in increased formation of peritoneal microvessels and lymphatic microvessels, playing pivotal roles in the development of UFF.
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Jiao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China.
authors.forename: Zhangsuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, Henan, China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan, China. Electronic address: zzzdoctor@139.com.
authors.forename: Zhanzheng
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000502:physiology; D015314:Dialysis Solutions / Q000009:adverse effects*; D004195:Disease Models, Animal; D042583:Lymphangiogenesis / Q000187:drug effects; D042601:Lymphatic Vessels / Q000187:drug effects; D008297:Male; D055806:Microvessels / Q000187:drug effects; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000201:enzymology / Q000209:etiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000502:physiology
chemical_list: D015314:Dialysis Solutions; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C467498:vascular endothelial growth factor A, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: COX-2; Celecoxib; Peritoneal dialysis; Ultrafiltration failure; VEGF