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.


CONCLUSIONS
ACE inhibitors, such as captopril, may be applied as important compounds for MMP-2 inhibition in inflammation caused by CAPD.
Yamamoto
Daisuke
D
Biomedical Computation Center, Osaka Medical College, 2-7 Daigakuchou, Takatuski, 569-8686, Japan. center@art.osaka-med.ac.jp
Takai
Shinji
S
Hirahara
Ichiro
I
Kusano
Eiji
E
D001202:Ascitic Fluid / Q000201:enzymology*; D055162:Biocatalysis / Q000187:drug effects*; D002216:Captopril / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020134:Catalytic Domain; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D010531:Peritoneal Dialysis, Continuous Ambulatory; D056627:Peritoneal Fibrosis / Q000188:drug therapy; D011485:Protein Binding
D061965:Matrix Metalloproteinase Inhibitors; D002216:Captopril; D020778:Matrix Metalloproteinase 2