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Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

BACKGROUNDIncreased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVETo verify the effect... Full description

Journal Title: PloS one 2013, Vol.8(7), p.e69309
Main Author: Gao, Jin-Hang
Other Authors: Wen, Shi-Lei , Yang, Wen-Juan , Lu, Yao-Yao , Tong, Huan , Huang, Zhi-Yin , Liu, Zhang-Xu , Tang, Cheng-Wei
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 1932-6203 ; DOI: 10.1371/journal.pone.0069309
Link: http://search.proquest.com/docview/1418647427/?pq-origsite=primo
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title: Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.
format: Article
creator:
  • Gao, Jin-Hang
  • Wen, Shi-Lei
  • Yang, Wen-Juan
  • Lu, Yao-Yao
  • Tong, Huan
  • Huang, Zhi-Yin
  • Liu, Zhang-Xu
  • Tang, Cheng-Wei
subjects:
  • Angiogenesis Inhibitors–Pharmacology
  • Animals–Therapeutic Use
  • Celecoxib–Complications
  • Disease Models, Animal–Drug Therapy
  • Hypertension, Portal–Physiopathology
  • Kidney–Drug Effects
  • Liver Cirrhosis–Pathology
  • Male–Physiopathology
  • Neovascularization, Pathologic–Complications
  • Pyrazoles–Drug Therapy
  • Rats–Physiopathology
  • Rats, Sprague-Dawley–Complications
  • Signal Transduction–Drug Therapy
  • Sulfonamides–Physiopathology
  • Thioacetamide–Pharmacology
  • Thioacetamide–Therapeutic Use
  • Thioacetamide–Drug Effects
  • Thioacetamide–Pharmacology
  • Thioacetamide–Therapeutic Use
  • Angiogenesis Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Thioacetamide
  • Celecoxib
ispartof: PloS one, 2013, Vol.8(7), p.e69309
description: BACKGROUNDIncreased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVETo verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODSCirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. RESULTSCompared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 1932-6203 ; DOI: 10.1371/journal.pone.0069309
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleCelecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.
creatorGao, Jin-Hang ; Wen, Shi-Lei ; Yang, Wen-Juan ; Lu, Yao-Yao ; Tong, Huan ; Huang, Zhi-Yin ; Liu, Zhang-Xu ; Tang, Cheng-Wei
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subjectAngiogenesis Inhibitors–Pharmacology ; Animals–Therapeutic Use ; Celecoxib–Complications ; Disease Models, Animal–Drug Therapy ; Hypertension, Portal–Physiopathology ; Kidney–Drug Effects ; Liver Cirrhosis–Pathology ; Male–Physiopathology ; Neovascularization, Pathologic–Complications ; Pyrazoles–Drug Therapy ; Rats–Physiopathology ; Rats, Sprague-Dawley–Complications ; Signal Transduction–Drug Therapy ; Sulfonamides–Physiopathology ; Thioacetamide–Pharmacology ; Thioacetamide–Therapeutic Use ; Thioacetamide–Drug Effects ; Thioacetamide–Pharmacology ; Thioacetamide–Therapeutic Use ; Angiogenesis Inhibitors ; Pyrazoles ; Sulfonamides ; Thioacetamide ; Celecoxib
descriptionBACKGROUNDIncreased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVETo verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODSCirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. RESULTSCompared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONSLong term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.
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titleCelecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.
descriptionBACKGROUNDIncreased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVETo verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODSCirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. RESULTSCompared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONSLong term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.
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titleCelecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.
authorGao, Jin-Hang ; Wen, Shi-Lei ; Yang, Wen-Juan ; Lu, Yao-Yao ; Tong, Huan ; Huang, Zhi-Yin ; Liu, Zhang-Xu ; Tang, Cheng-Wei
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abstractBACKGROUNDIncreased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVETo verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODSCirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. RESULTSCompared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONSLong term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.
doi10.1371/journal.pone.0069309
urlhttp://search.proquest.com/docview/1418647427/
date2013-01-01