Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy.
BACKGROUND: Matrix metalloproteinase (MMP)-2 plays an important role in tissue remodeling related to inflammation during continuous ambulatory peritoneal dialysis (CAPD) therapy. But its inhibitors were not applied clinically. We determined whether an angiotensin-converting enzyme (ACE) inhibitor, captopril, inhibits MMP-2 activity in peritoneal effluents from patients on CAPD, and simulated molecular models of the MMP-2-captopril complex. METHODS: The inhibitory effect of captopril on MMP-2 activity was measured in peritoneal effluents from 17 patients on CAPD. Molecular models of the MMP-2-captopril complex were simulated by 1000 iterations of random docking and energy minimization. RESULTS: Captopril directly inhibited MMP-2 activity in peritoneal effluents from patients on CAPD (IC50; 48 micromol/l), and that captopril binding to the MMP-2 active site could be formed in each complex model without molecular distortion. CONCLUSION: ACE inhibitors, such as captopril, may be applied as important compounds for MMP-2 inhibition in inflammation caused by CAPD.
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GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
MMP-2 Matrix metalloproteinase (MMP)-2 angiotensin-converting enzyme ACE MMP-2 MMP-2 MMP-2 MMP-2 MMP-2 MMP-2 angiotensin ACE matrix metalloproteinase-2 captopril captopril captopril captopril Captopril captopril captopril Captopril