Effects of antisecretory agents on angiogenesis during healing of gastric ulcers.
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.
Akimoto
Masumi
M
Institute of Geriatrics, Tokyo Women's Medical University, 2-15-1 Shibuya, Shibuya-ku, Tokyo, 150-0002, Japan.
Hashimoto
Hiroshi
H
Shigemoto
Mutsuo
M
Maeda
Atsushi
A
Yamashita
Katsuko
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001483:Base Sequence; D001562:Benzimidazoles / Q000627:therapeutic use*; D001707:Biopsy, Needle; D016022:Case-Control Studies; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology; D005773:Gastroscopy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016567:Nizatidine / Q000008:administration & dosage*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D064750:Rabeprazole; D019718:Receptors, CXCR4 / Q000378:metabolism; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D064750:Rabeprazole; D009853:Omeprazole; D016567:Nizatidine