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Updated: Jun 21, 2026
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Active matrix metalloproteinases 3 and 9 are independently associated with coronary artery in-stent restenosis
G T Jones1, G P Tarr, L V Phillips
1Vascular Research Group, Section of Surgery, University of Otago, Dunedin, New Zealand. greg.jones@otago.ac.nz
Objective:
This study aimed to determine whether plasma levels of active matrix metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New Zealand patients treated with bare-metal coronary stents.
Methods:
A group of 152 patients with a history of ISR were compared with 151 symptom free 1-year post-stenting patients (non-ISR). Demographic and angiographic characteristics were collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based isoform sensitive assays.
Results:
Both active MMP-9 and active MMP-3 were independently associated with history of ISR. Elevated levels of both active MMP-3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for association with ISR, with 37% of ISR patients having such levels versus 11% on non-ISR. The addition of both of the MMP biomarkers significantly increased the area under the curve (AUC) of a receiver operator characteristic (ROC) analysis incorporating the significant demographic and angiographic variables (AUC 0.85 versus 0.78, p<0.005).
Conclusion:
Measures of plasma active MMP isoforms appear to be independently associated with ISR, and assessment of multiple MMP markers yields cumulative utility.
Insights
Plasma levels of active matrix metalloproteinases (MMP), specifically MMP-3 and MMP-9, predict in-stent restenosis (ISR) after coronary stent placement. Elevated levels of these MMPs significantly increase the risk of ISR development.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Interventional Cardiology
Background:
- In-stent restenosis (ISR) remains a significant complication following coronary stent implantation.
- Identifying reliable predictors of ISR is crucial for improving patient outcomes and guiding treatment strategies.
Purpose of the Study:
- To investigate whether plasma levels of active matrix metalloproteinases (MMP) serve as predictors for in-stent restenosis (ISR).
- To assess the association between specific active MMP isoforms (MMP-1, -2, -3, -9) and ISR in patients receiving bare-metal coronary stents.
Main Methods:
- A case-control study comparing 152 patients with ISR history to 151 asymptomatic 1-year post-stenting patients (non-ISR).
- Plasma concentrations of active MMP-1, -2, -3, -9, and TIMP-1 were quantified using sensitive ELISA assays.
- Demographic and angiographic data were collected for all participants.
Main Results:
- Active MMP-9 and MMP-3 were independently associated with a history of ISR.
- Elevated levels of both active MMP-3 and MMP-9 showed a strong association with ISR (OR 11.8, p<0.0001), present in 37% of ISR patients vs. 11% of non-ISR patients.
- Incorporating MMP biomarkers significantly improved the predictive accuracy (AUC 0.85 vs. 0.78) in ROC analysis.
Conclusions:
- Plasma levels of active MMP isoforms are significant independent predictors of ISR.
- Assessing multiple MMP markers demonstrates cumulative utility in predicting ISR, enhancing diagnostic capability.
