J Korean Gastric Cancer Assoc.  2005 Sep;5(3):191-199.

Suppression of Helicobacter pylori-induced Angiogenesis by a Gastric Proton Pump Inhibitor

• Jin SH
• Lee HY
• Kim DK
• Cho YK
• Hahm KB
• Han SU

Abstract

BACKGROUND
Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy.
MATERIALS AND METHODS
A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of HIF-1alpha and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay.
RESULTS
H. pylori-associated gastritis tissues showed significantly higher density of CD34+ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of HIF-1alpha. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis.
CONCLUSION
The fact that PPIs can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

Keyword

Helicobacter pylori; Gastric cancer; Carcinogenesis; Angiogenesis; Proton pump inhibitor

MeSH Terms

Blood Vessels
Carcinogenesis
Culture Media, Conditioned
Gastric Mucosa
Gastritis
Helicobacter pylori
Helicobacter*
Human Umbilical Vein Endothelial Cells
Humans
Phosphorylation
Phosphotransferases
Proton Pumps*
Protons*
Stomach Neoplasms
Vascular Endothelial Growth Factor A
Culture Media, Conditioned
Phosphotransferases
Proton Pumps
Protons
Vascular Endothelial Growth Factor A