Angiogenesis in gastric ulcers: impaired in patients taking non-steroidal anti-inflammatory drugs.
Non-steroidal anti-inflammatory drug (NSAID) therapy is associated with delayed gastroduodenal ulcer healing. In rats the degree of angiogenesis (new vessel formation) within the ulcer bed correlates strongly with the extent and speed of ulcer healing and may be inhibited by NSAIDs. This study therefore assessed the vascularity of 38 antral gastric ulcers immunohistochemically, using CD31 a vascular endothelial cell marker, in 17 patients taking NSAIDs and 19 control patients. In the superficial granulation tissue NSAID therapy was associated with a significant reduction in the median number of capillaries (13.5 (IQR: 9.5-18) v 23.5 (14-31) (p < 0.005)), number of vessel buds (6 (4-12.5) v 17 (12-23) (p < 0.05)), and maximum vessel diameter (29 (20.75-30.75) v 33.75 (24-45) (p < 0.05)) when compared with controls. In deep granulation tissue NSAID therapy was similarly associated with a significant reduction in the number of capillaries (9 (6.5-12) v 14 (9-19.25) (p < 0.04)), number of vessel buds (5 (3.5-8.5) v 13 (7-16.5) (p < 0.01)), and maximum vessel diameter (23 (18-20.5) v 33 (21.5-45) (p < 0.02)). There were no differences in vascularity in the adjacent glandular mucosa. Impairment of angiogenesis may be an important mechanism of NSAID related delayed ulcer healing.
Hudson
N
N
Division of Gastroenterology, University Hospital, Nottingham.
Balsitis
M
M
Everitt
S
S
Hawkey
C J
CJ
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013276:Stomach Ulcer / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1