Skip to main content

Advertisement

Log in

Effects of antisecretory agents on angiogenesis during healing of gastric ulcers

  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

We studied the effects of a proton pump inhibitor (PPI) and an H2-receptor antagonist (H2-blocker) on angiogenesis during gastric ulcer healing, by examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4 (CXCR4) expression in the gastric mucosa.

Methods

Patients with gastric ulcers were allocated to an untreated control group, consisting of patients with active ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given rabeprazole at 20 mg/day), or an H2-blocker group (H; given nizatidine at 800 mg/day). Frozen sections of biopsy specimens were examined by reverse transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA.

Results

CXCR4 mRNA levels were elevated in the control (GH and GS patients) group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA subgroup of the PPI group (P < 0.01), but its level decreased with time.

Conclusions

In the PPI group, CXCR4 levels were increased in the early phase of ulcer healing and returned to a level similar to that in the control group during the scar phase. These results suggest that PPIs increase the expression of CXCR4 mRNA and thus promote vessel regeneration and maturation, facilitating ulcer healing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. K Tachibana S Hirota T Nagasawa et al. (1998) ArticleTitleThe chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract Nature 398 591–4

    Google Scholar 

  2. F Mirshahi J Pourtau H Li et al. (2000) ArticleTitleSDF-1 activity on microvascular endothelial cells. Consequences on angiogenesis in in vitro and in vivo models Thromb Res 99 587–94 Occurrence Handle10.1016/S0049-3848(00)00292-9 Occurrence Handle10974345

    Article  PubMed  Google Scholar 

  3. NJ Jordan G Kolios SE Abbot et al. (1999) ArticleTitleExpression of functional CXCR4 chemokine receptors on human colonic epithelial cells J Clin Invest 104 1061–9 Occurrence Handle10525044

    PubMed  Google Scholar 

  4. M Akimoto H Hashimoto M Shigemoto et al. (1999) ArticleTitleThe roles of angiogenetic factors (stromal-cell-derived factor-1 and vascular endothelial growth factor) in ulcer healing (abstract Gastroenterology 116 110

    Google Scholar 

  5. M Akimoto H Hashimoto M Shigemoto et al. (2001) ArticleTitleEffects of antisecretory agents on angiogenesis during healing of gastric ulcers (abstract) Gastroenterology 120 148

    Google Scholar 

  6. M Akimoto H Hashimoto M Shigemoto et al. (2002) ArticleTitleRoles of angiogenic factors and endothelin-1 in gastric ulcer healing Clin Sci (Lond) 103 IssueIDSuppl 1 450S–4

    Google Scholar 

  7. A Iwasaki R Kurihara T Hirai et al. (1999) ArticleTitleEffect of proton pump inhibitor, rabeprazole, on gastric acid secretion Jpn Pharmacol Ther 27 705–13

    Google Scholar 

  8. H Fujisaki H Shibata K Oketani et al. (1991) ArticleTitleInhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione Biochem Pharmacol 42 321–8 Occurrence Handle1650210

    PubMed  Google Scholar 

  9. AK Ghosh N Hirasawa K Ohuchi (2001) ArticleTitleEnhancement by histamine of vascular endothelial growth factor production in granulation tissue via H2 receptor Br J Pharmacol 134 1419–28 Occurrence Handle10.1038/sj.bjp.0704372 Occurrence Handle11724747

    Article  PubMed  Google Scholar 

  10. Tsuchida T, Tsukamoto Y, Segawa K, et al. Effects of cimetidine and omeprazole on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers in rats. Digestion 47:8–14

  11. H Fujisaki H Shibata K Oketani et al. (1991) ArticleTitleEffects of the proton pump inhibitor, E3810, on gastric secretion and gastric and duodenal ulcers or erosions in rats Drug Invest 3 328–32

    Google Scholar 

  12. T Ishizaki Y Horai (1999) ArticleTitleCytochrome P450 and the metabolism of proton pump inhibitors—emphasis on rabeprazole Aliment Pharmacol Ther 13 IssueIDSuppl 3 27–36 Occurrence Handle10.1046/j.1365-2036.1999.00022.x

    Article  Google Scholar 

  13. K Adachi T Katsube A Kawamura et al. (2000) ArticleTitleCYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole Aliment Pharmacol Ther 14 1259–66 Occurrence Handle11012469

    PubMed  Google Scholar 

  14. C Feil HG Augustin (1998) ArticleTitleEndothelial cells differentially express functional CXCR-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenenous cytokines Biochem Biophys Res Commun 247 38–45 Occurrence Handle10.1006/bbrc.1998.8499 Occurrence Handle9636650

    Article  PubMed  Google Scholar 

  15. S Tsuji S Kawano M Tsujii et al. (1998) ArticleTitleMucosal microcirculation and angiogenesis in gastrointestinal tract Jpn J Clin Med 56 39–44

    Google Scholar 

  16. JH Wandall (1992) ArticleTitleEffects of omeprazole on neutrophil chemotaxis, superoxide production, degranulation, and translocation of cytochrome b-245 Gut 33 617–21 Occurrence Handle1319381

    PubMed  Google Scholar 

  17. M Suzuki M Mori S Miura et al. (1996) ArticleTitleOmeprazole attenuates oxygen-derived free radical production from human neutrophils Free Radic Biol Med 21 727–31 Occurrence Handle10.1016/0891-5849(96)00180-3 Occurrence Handle8891677

    Article  PubMed  Google Scholar 

  18. D Lapenna S de Gioia G Ciofani et al. (1996) ArticleTitleAntioxidant properties of omeprazole FEBS Lett 382 189–92 Occurrence Handle10.1016/0014-5793(96)00155-X Occurrence Handle8612750

    Article  PubMed  Google Scholar 

  19. RD Mc Cabe DB Young (1992) ArticleTitleEvidence of a K(+)-H(+)-ATPase in vascular smooth muscle cells Am J Physiol 262 H1955–8 Occurrence Handle1320341

    PubMed  Google Scholar 

  20. SP Marrelli X Zhao JC Allen (1997) ArticleTitleMolecular evidence for a vascular smooth muscle H+-K+-ATPase Am J Physiol 272 H869–74 Occurrence Handle9124450

    PubMed  Google Scholar 

  21. S Ombretta Y Lei V Sabrina et al. (2002) ArticleTitleRegulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1 Blood 99 2703–11 Occurrence Handle10.1182/blood.V99.8.2703 Occurrence Handle11929756

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akimoto, M., Hashimoto, H., Shigemoto, M. et al. Effects of antisecretory agents on angiogenesis during healing of gastric ulcers. J Gastroenterol 40, 685–689 (2005). https://doi.org/10.1007/s00535-005-1611-2

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-005-1611-2

Key words

Navigation