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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. 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. 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. ACE inhibitors, such as captopril, may be applied as important compounds for MMP-2 inhibition in inflammation caused by CAPD. Copyright 2010 Elsevier B.V. All rights reserved.

Citation

Daisuke Yamamoto, Shinji Takai, Ichiro Hirahara, Eiji Kusano. Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy. Clinica chimica acta; international journal of clinical chemistry. 2010 May 2;411(9-10):762-4

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PMID: 20184869

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