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Published on: May 8, 2017
Serum MMP-9 and TIMP-1 concentrations and MMP-9 activity during surgery-induced inflammation in humans
Johanna Helmersson-Karlqvist1, Torbjörn Akerfeldt, Lena Gunningberg
1Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden. johanna.helmersson_karlqvist@medsci.uu.se
Background:
Matrix metalloproteinase 9 (MMP-9) and the endogenous inhibitor to MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), have important roles in tissue remodelling and are implicated in a number of diseases related to inflammation. The time course in activation and formation of MMPs and TIMPs during an inflammatory reaction is not fully known. This study investigates MMP-9 and TIMP-1 concentrations and MMP-9 activity at different time points after major surgery when a state of noticeable inflammation is expected.
Methods:
Serum MMP-9 and TIMP-1 concentrations and MMP-9 activity were analysed preoperatively and 4 and 30 days postoperatively in patients undergoing elective surgery (coronary artery bypass n=21; orthopaedic surgery, n=29).
Results:
Serum TIMP-1 and MMP-9 activity increased significantly 4 days after surgery (p<0.05 and p<0.01, respectively) and decreased again 30 days after surgery (p<0.01, respectively, compared to 4 days after surgery). Serum MMP-9 increased significantly 4 days after surgery (p<0.05) and was still high 30 days after surgery (p<0.01 compared to before surgery). The calculated MMP-9/TIMP-1 ratio was increased 30 days after surgery compared to before surgery (p<0.01).
Conclusions:
The inflammatory state induced by elective surgery is associated with increased TIMP-1 response and MMP-9 activity in serum within a few days which may be of importance for the postoperative heeling process. The further increase in MMP-9 concentrations at day 30 postoperative did not result in increased MMP-9 activity. Serum MMP-9 concentrations or the calculated MMP-9/TIMP-1 ratio do not entirely represent MMP-9 activity during surgery-induced inflammation.
Insights
Post-surgery inflammation involves increased matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) activity. While MMP-9 levels remain high, its activity doesn't correlate with concentrations 30 days post-operation.
Area of Science:
- Biochemistry
- Immunology
- Surgical Research
Background:
- Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are key regulators of tissue remodeling.
- Their roles in inflammation and disease are established, but their temporal dynamics during inflammatory responses remain unclear.
Purpose of the Study:
- To investigate the time course of MMP-9 and TIMP-1 concentrations and MMP-9 activity following major elective surgery.
- To understand the relationship between these markers and the inflammatory state induced by surgery.
Main Methods:
- Serum samples were collected from patients undergoing coronary artery bypass (n=21) or orthopedic surgery (n=29) preoperatively, and 4 and 30 days postoperatively.
- MMP-9 and TIMP-1 concentrations, along with MMP-9 activity, were analyzed at these time points.
Main Results:
- Serum TIMP-1 and MMP-9 activity significantly increased by day 4 post-surgery, then decreased by day 30.
- Serum MMP-9 concentrations also increased significantly by day 4 and remained elevated at day 30.
- The MMP-9/TIMP-1 ratio was significantly higher 30 days post-surgery compared to pre-surgery.
Conclusions:
- The inflammatory response to elective surgery involves a transient increase in TIMP-1 and MMP-9 activity within days, potentially aiding healing.
- Elevated MMP-9 concentrations at 30 days post-surgery did not correspond to increased MMP-9 activity.
- Serum MMP-9 levels or the MMP-9/TIMP-1 ratio may not fully reflect MMP-9 activity during surgery-induced inflammation.
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