# Time trajectories and within-subject correlations of matrix metalloproteinases 3, 8, 9, 10, 12, and 13 serum levels and their ability to predict mortality in polytraumatized patients: a pilot study

**Authors:** Lukas L. Negrin, Greta L. Carlin, Robin Ristl, Stefan Hajdu

PMC · DOI: 10.1186/s40001-024-01775-x · 2024-04-10

## TL;DR

This pilot study explores how specific matrix metalloproteinase (MMP) serum levels change over time in polytrauma patients and their potential to predict survival.

## Contribution

The study identifies time-dependent patterns of MMP levels and suggests that MMP10 may predict mortality in polytraumatized patients.

## Key findings

- MMP8, MMP9, and MMP12 levels showed similar time trajectories and strong correlations after polytrauma.
- MMP10 levels at admission were a predictor of in-hospital mortality, with higher levels associated with lower odds of death.
- MMP3, MMP10, and MMP13 levels increased initially but decreased later, showing synchronized patterns.

## Abstract

Managing polytrauma victims poses a significant challenge to clinicians since applying the same therapy to patients with similar injury patterns may result in different outcomes. Using serum biomarkers hopefully allows for treating each multiple injured in the best possible individual way. Since matrix metalloproteinases (MMPs) play pivotal roles in various physiological processes, they might be a reliable tool in polytrauma care.

We evaluated 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and stayed at the intensive care unit for at least one night. We determined their MMP3, MMP8, MMP9, MMP10, MMP12, and MMP13 serum levels at admission (day 0) and on days 1, 3, 5, 7, and 10.

Median MMP8, MMP9, and MMP12 levels immediately rose after the polytrauma occurred; however, they significantly decreased from admission to day 1 and significantly increased from day 1 to day 10, showing similar time trajectories and (very) strong correlations between each two of the three enzyme levels assessed at the same measurement point. For a two-day lag, autocorrelations were significant for MMP8 (− 0.512) and MMP9 (− 0.302) and for cross-correlations between MMP8 and MMP9 (− 0.439), MMP8 and MMP12 (− 0.416), and MMP9 and MMP12 (− 0.307). Moreover, median MMP3, MMP10, and MMP13 levels significantly increased from admission to day 3 and significantly decreased from day 3 to day 10, showing similar time trajectories and an (almost) strong association between every 2 levels until day 7. Significant cross-correlations were detected between MMP3 and MMP10 (0.414) and MMP13 and MMP10 (0.362). Finally, the MMP10 day 0 level was identified as a predictor for in-hospital mortality. Any increase of the MMP10 level by 200 pg/mL decreased the odds of dying by 28.5%.

The time trajectories of the highly varying individual MMP levels elucidate the involvement of these enzymes in the endogenous defense response following polytrauma. Similar time courses of MMP levels might indicate similar injury causes, whereas lead–lag effects reveal causative relations between several enzyme pairs. Finally, MMP10 abundantly released into circulation after polytrauma might have a protective effect against dying.

## Linked entities

- **Proteins:** MMP3 (matrix metallopeptidase 3), MMP8 (matrix metallopeptidase 8), MMP9 (matrix metallopeptidase 9), MMP10 (matrix metallopeptidase 10), MMP12 (matrix metallopeptidase 12), MMP13 (matrix metallopeptidase 13)

## Full-text entities

- **Genes:** MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321] {aka HME, ME, MME, MMP-12}, MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317] {aka CLG1, HNC, MMP-8, PMNL-CL}, MMP10 (matrix metallopeptidase 10) [NCBI Gene 4319] {aka SL-2, STMY2}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}
- **Diseases:** polytrauma (MESH:D009104), trauma (MESH:D014947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11005259/full.md

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Source: https://tomesphere.com/paper/PMC11005259