Reduced tissue type plasminogen activator activity of the gastroduodenal mucosa in peptic ulcer disease.
The gastroduodenal mucosa has a rich blood supply. An active fibrinolytic system is presumably required to maintain vascular patency, and impairment may result in reduced blood flow, focal tissue necrosis, and peptic ulcerogenesis. Tissue type and urokinase type plasminogen activator activity (expressed as mIU/mg protein) and plasminogen activator inhibitor type-1 antigen were assayed in homogenates of gastric and duodenal biopsy specimens taken from patients with: normal endoscopy (controls) (n = 14); active duodenal ulcer (n = 21); healed duodenal ulcer (n = 12); and active benign gastric ulcer (n = 15). In controls mean duodenal tissue type plasminogen activator activity was 4110 and urokinase type plasminogen activator activity 150; gastric tissue type plasminogen activator was 2760 and urokinase type plasminogen activator 170; plasminogen activator inhibitor type-1 was generally undetectable. At the edge of active duodenal ulcers tissue type plasminogen activator was considerably reduced, 2220 (p < 0.001) whereas urokinase type plasminogen activator was raised, 290 (p < 0.01). At the edge of active benign gastric ulcers tissue type plasminogen activator was substantially reduced, 1160 (p < 0.001) but urokinase type plasminogen activator was unchanged. At the scar of healed duodenal ulcers tissue type plasminogen activator was slightly reduced, 3290, but urokinase type plasminogen activator was increased, 308 (p < 0.05). H2 receptor antagonist treatment had little effect on tissue type or urokinase type plasminogen activator activity. Plasminogen activator inhibitor type-1 was increased at the edge of active ulcers (p < 0.05) especially when tissue type plasminogen activity was low (r = -0.61, p < 0.05). These findings are consistent with the hypothesis that impaired fibrinolytic activity may be implicated in peptic ulcerogenesis.
Wodziński
M A
MA
Northern General Hospital, Sheffield.
Bardhan
K D
KD
Reilly
J T
JT
Cooper
P
P
Preston
F E
FE
D004381:Duodenal Ulcer / Q000201:enzymology*; D005342:Fibrinolysis; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013276:Stomach Ulcer / Q000201:enzymology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator