PMID- 16127019
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20181113
IS  - 0017-5749 (Print)
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 55
IP  - 1
DP  - 2006 Jan
TI  - Novel action of gastric proton pump inhibitor on suppression of Helicobacter 
      pylori induced angiogenesis.
PG  - 26-33
AB  - BACKGROUND: Although activation of mitogen activated protein kinases (MAPKs) by 
      Helicobacter pylori infection is associated with induction of host angiogenesis, 
      which may contribute to H pylori associated gastric carcinogenesis, the strategy 
      for its prevention has not been identified. As we previously reported a strong 
      inhibitory action of gastric proton pump inhibitors (PPIs) on MAPK extracellular 
      signal regulated kinase (ERK)1/2 phosphorylation, we investigated whether PPIs 
      could suppress the H pylori induced angiogenesis via inhibition of MAPK ERK1/2. 
      METHODS: To address the relationship between H pylori infection and angiogenesis, 
      comparative analysis of density of CD34(+) blood vessel was performed in tissues 
      obtained from 20 H pylori positive gastritis and 18 H pylori negative gastritis 
      patients. Expression of hypoxia inducible factor 1 (HIF-1alpha) and vascular 
      endothelial growth factor (VEGF) was tested by reverse transcription-polymerase 
      chain reaction and secretion of interleukin 8, and VEGF was measured by ELISA. To 
      evaluate the direct effect of H pylori infection on the tubular formation of 
      human umbilical vein endothelial cells (HUVEC), an in vitro angiogenesis assay 
      was employed. Activation of MAPK and nuclear factor kappaB (NFkappaB) was 
      detected by immunoblotting. RESULTS: H pylori positive gastritis patients showed 
      a higher density of CD34(+) blood vessels (mean 40.9 (SEM 4.4)) than H pylori 
      negative gastritis patients (7.2+/-0.8), which was well correlated with 
      expression of HIF-1alpha. Conditioned media from H pylori infected gastric 
      epithelial cells directly induced tubular formation of HUVEC and the increase of 
      in vitro angiogenesis was suppressed by PPI treatment. Infection of H pylori 
      significantly upregulated expression of HIF-1alpha and VEGF in gastric epithelial 
      cells and expression of proangiogenic factors was mediated by MAPK activation and 
      partially responsible for NFkappaB activation. PPIs effectively inhibited the 
      phosphorylation of MAPK ERK1/2 that is a principal signal for H pylori induced 
      angiogenesis. CONCLUSIONS: The fact that PPIs could downregulate H pylori induced 
      angiogenesis indicates that antiangiogenic treatment using a PPI could be a 
      promising protective therapeutic approach for H pylori associated carcinogenesis.
FAU - Yeo, M
AU  - Yeo M
AD  - Genome Research Centre for Gastroenterology, Ajou University Medical Centre, San 
      5, Wonchon-dong, Yeongtong-gu, Suwon, 442-749, Korea. marie8346@hotmail.com
FAU - Kim, D-K
AU  - Kim DK
FAU - Han, S U
AU  - Han SU
FAU - Lee, J E
AU  - Lee JE
FAU - Kim, Y B
AU  - Kim YB
FAU - Cho, Y K
AU  - Cho YK
FAU - Kim, J H
AU  - Kim JH
FAU - Cho, S W
AU  - Cho SW
FAU - Hahm, K-B
AU  - Hahm KB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050826
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Antigens, CD34)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Proton Pump Inhibitors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adult
MH  - Angiogenesis Inducing Agents/metabolism
MH  - Angiogenesis Inhibitors/pharmacology
MH  - Anti-Ulcer Agents/pharmacology
MH  - Antigens, CD34/analysis
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Endothelium, Vascular/drug effects/microbiology
MH  - Gastric Mucosa/blood supply
MH  - Gastritis/complications/metabolism/microbiology
MH  - Helicobacter Infections/*complications/metabolism
MH  - *Helicobacter pylori
MH  - Humans
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Neovascularization, Pathologic/metabolism/*microbiology/pathology
MH  - *Proton Pump Inhibitors
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
PMC - PMC1856363
COIS- Conflict of interest: None declared.
EDAT- 2005/08/30 09:00
MHDA- 2006/01/19 09:00
PMCR- 2009/01/01
CRDT- 2005/08/30 09:00
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
PHST- 2009/01/01 00:00 [pmc-release]
AID - gut.2005.067454 [pii]
AID - gt67454 [pii]
AID - 10.1136/gut.2005.067454 [doi]
PST - ppublish
SO  - Gut. 2006 Jan;55(1):26-33. doi: 10.1136/gut.2005.067454. Epub 2005 Aug 26.