Matrix metalloproteinase‐2 inhibition by temocapril and its important role in peritoneal transport

Abstract

1. Matrix metalloproteinase (MMP)-2 plays an important role in tissue remodelling during peritoneal injury caused by peritoneal dialysis (PD), but MMP-2 inhibitors have not yet been used clinically. Recently, it was reported that captopril, an angiotensin-converting enzyme inhibitor (ACEI), can inhibit MMP-2. 2. To investigate the potential usefulness of ACEI during PD, the molecular interaction between the MMP-2 active site and the active form of temocapril (temocaprilat) was investigated using molecular modelling. Furthermore, the effects of temocapril on MMP-2 activity in peritoneal effluents and the peritoneal solute transport rate of PD patients were determined. 3. Temocaprilat bound to the MMP-2 active centre and recognized two hydrophobic substrate-binding sites in the MMP-2 molecular model. Matrix metalloproteinase-2 activity in peritoneal effluents was directly inhibited by temocaprilat (IC(50) 0.47 μmol/L). In one patient given temocapril, the peritoneal solute transport rate decreased gradually during PD. 4. Temocapril may prove to be an important candidate for development as a novel therapeutic agent for MMP-2 inhibition to prevent peritoneal injury caused by PD.

Recent Understanding and Future Directions in the Application of MMP-2 in Encapsulating Peritoneal Sclerosis Clinical Practice

“…and the conclusion was confirmed by a multicenter study in The Netherlands [41]. Renin-angiotensin system inhibition and peroxisome proliferator-activated receptor agonist have also played a role in EPS therapy, and studies have shown that they can inhibit the activity of MMP-2 in peritoneal dialyzate and alleviate the accumulation and fibrosis of extraperitoneal matrix to some extent [42][43][44]. Perhaps MMP-2 is not only a diagnostic biomarker but also a potential therapeutic target.…”