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Published on: March 30, 2022
Dynamic changes of matrix metalloproteinases and their tissue inhibitors in severe sepsis
Diána Mühl1, Bálint Nagy, Gábor Woth
1Department of Anesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary. drdianamuhl@gmail.com
Purpose:
Little is known about the dynamic changes of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in sepsis. Our aim was therefore to investigate the time course of MMPs and their inhibitors in patients experiencing severe sepsis.
Methods:
Our prospective controlled analysis included 38 patients with severe sepsis. Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured daily at a 5-day-long period with enzyme-linked immunosorbent assay. Seventeen healthy volunteers were invited as controls.
Results:
MMP-2 showed no difference compared to controls, whereas significantly elevated MMP-9 levels were detected on admission (P < .005). Significantly elevated but declining TIMP-1 levels were measured during the whole trial (P < .002-.004). Except for the second day, TIMP-2 levels were significantly lower than controls (P < .05-.009). MMP2/TIMP-1 ratios were significantly lower in septic patients (P < .03-.006), whereas MMP-2/TIMP-2 ratios were elevated throughout our study (P < .03-.006). MMP-9/TIMP-1 ratios were significantly lower at the first 3 days (P < .05-.008). MMP-9/TIMP-2 was significantly elevated on admission (P < .006).
Conclusions:
Our research is the first follow-up study dealing with MMPs, TIMPs, and their ratios in severe sepsis. Our results indicate that MMPs and TIMPs may play a crucial role in severe sepsis, especially TIMP-1, MMP-9, and possibly TIMP-2, after an extensive study.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) show dynamic changes in severe sepsis. Elevated MMP-9 and altered MMP/TIMP ratios suggest their crucial role in sepsis progression.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening condition with complex pathophysiological mechanisms.
- The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in sepsis pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the dynamic changes and time course of MMPs and TIMPs in patients with severe sepsis.
- To analyze the ratios between MMPs and TIMPs in the context of severe sepsis.
Main Methods:
- Prospective controlled study involving 38 severe sepsis patients and 17 healthy controls.
- Daily measurement of plasma MMP-2, MMP-9, TIMP-1, and TIMP-2 levels over 5 days using ELISA.
- Analysis of MMP/TIMP ratios.
Main Results:
- MMP-9 levels were significantly elevated on admission in sepsis patients.
- TIMP-1 levels were elevated but declining, while TIMP-2 levels were generally lower than controls.
- Specific alterations in MMP-2/TIMP-1, MMP-2/TIMP-2, MMP-9/TIMP-1, and MMP-9/TIMP-2 ratios were observed.
Conclusions:
- This is the first follow-up study detailing MMPs, TIMPs, and their ratios in severe sepsis.
- MMPs and TIMPs, particularly TIMP-1, MMP-9, and TIMP-2, appear to play a significant role in severe sepsis.
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