Plasma MMP–2 and MMP–9 and their inhibitors TIMP-1 and TIMP-2 during human orthotopic liver transplantation

Abstract

Thromb Haemost 2004; 91: 506-13form. No release of MMP-2 from the graft could be detected. In contrast, plasma levels of MMP-9 increased sharply during the anhepatic and postreperfusion periods. Peak MMP-9 levels of about eight times above baseline were found at 30 minutes after reperfusion. Most MMP-9 appeared to be in its active/inhibitorcomplexed form. No significant differences were observed between the three treatment groups. However, in patients with more severe ischemia/reperfusion (I/R) injury the MMP-9 concentration, particularly of the active/inhibitor-complexed form, remained high at 120 minutes postreperfusion compared to patients with no or mild I/R injury. The decrease in plasma levels of MMP-2,TIMP-1 and TIMP-2 during OLT occurred irrespective of the severity of the I/R injury. There was a significant correlation between MMP-9 and t-PA levels, but not with TNF-α. In conclusion, OLT is associated with a sharp increase of MMP-9 during the anhepatic and postreperfusion periods, which coincided with the changes in t-PA. MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine-protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation. KeywordsAprotinin, ischemia/reperfusion injury, liver transplantation, matrix metalloproteinases, plasmin Summary Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases.We therefore studied the evolution of MMP-2 and -9 plasma concentrations during OLT and the effect of serine-protease inhibition by aprotinin on the level and activation of these MMPs. In a group of 24 patients who participated in a randomized, double-blind, placebo-controlled study we determined serial MMP-2 and MMP-9 plasma levels during transplantation using ELISA (total MMP), activity assays (activatable MMP) and zymography. In addition, the MMP-inhibitors TIMP-1 and TIMP-2 were assessed by ELISA. The putative regulating factors tumor necrosis factor alpha (TNF-α) and tissue-type plasminogen activator (t-PA) were assessed as well. Patients were administered high-dose aprotinin, regular-dose aprotinin or placebo during surgery. Plasma TIMP-1, TIMP-2 and MMP-2 level gradually decreased during transplantation. Approximately twothirds of total MMP-2 appeared to be in its activatable proMMP Correspondence to:

MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

“…In previous studies we demonstrated that MMP-9, but not MMP-2, could play an important role in immediate I/R injury [23] and in acute allograft rejection after liver transplantation [14]. In the present study we assessed the impact of the donor MMP genotypes on the outcome and complications after liver transplantation but no associations were found.…”

“…Differences in MMP levels according to the genotype and disease complications were assessed by the MannWhitney U or the Wilcoxon signed ranks test for nonparametric data [14,23]. MMP levels are expressed as mean ± S.E.M.…”

Covalent linking peptide to hydrothermally reduced graphene oxide for ultrasensitive detection of matrix metalloproteinase 9

“…Similarly, Nguyen and coworkers noncovalently bound fluorescent gold nanocluster-labeled peptide containing the specific cleavage site of MMP9 to GO for MMP9 detection, and the detection limit of this probe was 0.15 nM (Nguyen et al 2017). However, extremely low concentration of MMP9 in healthy human plasma, about tenfold lower than that of MMP2 (Kuyvenhoven et al 2004), makes MMP9 detection very difficult.…”

Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

“…Many researchers have focused on TIMP-1 and TIMP-2 during liver regeneration [25][26][27][28] . Some researchers have focused on postoperative behavior of TIMP-1 [28] .…”

“…Currently, four members have been identified in the TIMP family which can inhibit various MMPs [24] . In particular, many researchers have focused on TIMP-1 and TIMP-2 during liver regeneration [25][26][27][28] . Although shear stress with portal hypertension and CIWR injury trigger the liver regeneration cascade after liver surgery, these injuries also cause fatal liver damage [29][30][31] .…”