Plasma Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 as Prognostic Biomarkers in Critically Ill Patients.

Halina Jędrzejowska-Szypułka,Izabela Duda,Joana Lewin-Kowalik,Łukasz Krzych

doi:10.1515/med-2020-0008

Abstract

Matrix metalloproteinase 9 (MMP-9) plays an important role in inflammatory and pathological processes by enabling the inflow of leukocytes to the site of infection or tissue damage. MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) have been described as potential prognostic biomarkers in various clinical settings. The aim of the study was to evaluate the usefulness of plasma levels of MMP-9 and TIMP-1 as well as the MMP-9/ TIMP-1 ratio in predicting the outcome in patients admitted to the intensive care unit (ICU). The study included 56 critically ill patients with multiple organ failure. Plasma levels of MMP-9 and TIMP-1 were determined on hospitalization day 1, 2, 3 and 7. Nineteen (35.7%) patients died. The level of TIMP-1 was statistically significantly higher on day 1 and 7 of hospitalization in non-survivors, as compared to survivors (p=0.01). A statistically significant positive correlation was found between MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio was comparable in both groups during of observation (0.62 on day 1). The MMP-9/TIMP-1 ratio was positively correlated with the level of lactate and negatively correlated with platelet count. Likewise, TIMP-1 was positively correlated with the level of lactate. The level of MMP-9 was higher in the non-survivor group only on day 7 of observation. In conclusion, although TIMP-1 and MMP-9 concentrations were higher in non-survivors and the MMP-9/TIMP-1 ratio was related to some parameters of critical illness, further research is needed to verify whether they can serve as reliable biomarkers for early prognostication of ICU patients.

Highlights

The extracellular matrix (ECM) is a dynamic, elastic and compound structure that fills the area between cells [1]
Matrix metalloproteinases (MMPs) belong to the group of enzymes involved in the degradation of basilar membrane proteins and ECM, which in turn facilitates the migration of cells
The Matrix metalloproteinase 9 (MMP-9)/tissue inhibitor of metalloproteinase 1 (TIMP-1) ratio on day 1 was found to be negatively correlated with the duration of intensive care unit (ICU) stay (Table 3). 19 of 56 patients died resulting in a mortality rate of 35.7%

Summary

Introduction

The extracellular matrix (ECM) is a dynamic, elastic and compound structure that fills the area between cells [1]. Matrix metalloproteinases (MMPs) belong to the group of enzymes involved in the degradation of basilar membrane proteins and ECM, which in turn facilitates the migration of cells. Metalloproteinases are produced by the majority of connective tissue cells, leukocytes, macrophages, vascular endothelial cells and neoplastic cells. After their release into the extracellular matrix, MMPs remain inactive. Their activation occurs through the cleavage of cysteine mediated by some proteolytic enzymes (plasmin, thrombin) and already active MMPs. The activity of MMPs is inhibited by specific tissue inhibitors of metalloproteinase (TIMP-1 - TIMP-4) and non-specific plasma inhibitors

Objectives

Methods

Conclusion