Impaired fibrinolysis and increased protease levels in gastric and duodenal mucosa of patients with active duodenal ulcer.
OBJECTIVE
Cathepsin B and L (cysteine proteases), urokinase- and tissue-type plasminogen activators (serine proteases), and type-1 inhibitor are involved in gastric mucosal injury. We determined tissue protease levels in duodenal ulcer and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori infection, and use of H2-blockers.


METHODS
Endoscopic biopsies of antral and duodenal mucosa were obtained from 61 patients with active or healed duodenal ulcer and control subjects. Antigen concentrations were measured by ELISA.


RESULTS
Significantly higher levels of cathepsins, urokinase-type plasminogen activator, type-1 inhibitor, and significantly lower levels of tissue-type plasminogen activator were found in active ulcers. Bleeders had the highest cathepsins and urokinase-type plasminogen activator levels. Higher levels of urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were observed in Helicobacter pylori-positive patients.


CONCLUSIONS
Our results suggest that impaired fibrinolysis (tissue-type plasminogen activator), intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis (urokinase-type plasminogen activator and type-1 inhibitor) are involved in duodenal ulcer formation and healing.
Herszènyi
L
L
Cattedra Malattie Apparato Digerente, Istituto di Medicina Interna, Dipartimento di Medicina di Laboratorio, Università di Padova, Italy.
Plebani
M
M
Carraro
P
P
De Paoli
M
M
Cardin
R
R
Di Mario
F
F
Kusstatscher
S
S
Naccarato
R
R
Farinati
F
F
D000328:Adult; D000368:Aged; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004381:Duodenal Ulcer / Q000150:complications / Q000201:enzymology* / Q000382:microbiology; D004386:Duodenum / Q000201:enzymology* / Q000473:pathology; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005342:Fibrinolysis; D005753:Gastric Mucosa / Q000201:enzymology*; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D002403:Cathepsins; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L