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Updated: Mar 31, 2026
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Granulocytes in coronary thrombus evolution after myocardial infarction--time-dependent changes in expression of
Xiaofei Li1, Onno J de Boer1, Hanneke Ploegmaker1
1Department of Pathology, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands.
Background:
Remodeling of extracellular matrix is a key process during wound healing, which is strictly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)]. In this study, we evaluated intrathrombotic MMPs and TIMPs and their cellular origin during thrombus evolution after disruption of coronary atherosclerotic plaque.
Materials And Methods:
Thrombectomy materials (N=120) obtained from patients with acute myocardial infarction were histologically classified in three groups based on thrombus age: fresh (<1day), lytic (1-5days), or organized (>5days) thrombi; materials showing a heterogeneous composition were classified according to oldest part. Presence and cellular origin of MMPs (MMP-1, MMP-2, MMP-8, MMP-9, and MMP-14) and TIMPs (TIMP-1, TIMP-2, and TIMP-3) was evaluated with immunostains (double) and with polymerase chain reaction.
Results And Conclusion:
MMPs and TIMPs were present in all the thrombectomy samples. A distinct temporal change in extent and cellular origin of MMPs and TIMPs during thrombus evolution was observed. In the early (fresh and lytic) stages of thrombus, high numbers of neutrophilic granulocytes occupy the thrombus mass and produce large amounts of MMPs and TIMPs. However, with progression of thrombus evolution (organizing stage) and diminishment of neutrophil granulocytes, there is disappearance of MMP-8 and MMP-9, steep decline of MMP-1 and TIMP-2, and progressive decrease of TIMP-3. In contrast, intrathrombotic MMP-2 and MMP-14 are present at a constant high level during the entire process of thrombus evolution. These temporal changes indicate a complex time-dependent function of MMPs, which are largely granulocyte derived, in the healing process of thrombus after plaque disruption.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) play a dynamic role in thrombus healing. Neutrophils initially produce high levels of MMPs and TIMPs, with levels changing as the thrombus evolves.
Area of Science:
- Cardiovascular Biology
- Wound Healing Research
- Thrombosis and Hemostasis
Background:
- Extracellular matrix remodeling is crucial for wound healing, regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
- Understanding intrathrombotic MMPs and TIMPs and their cellular origins is vital for thrombus evolution after coronary plaque disruption.
Purpose of the Study:
- To evaluate intrathrombotic MMPs and TIMPs and their cellular origin during thrombus evolution.
- To investigate the temporal changes in MMPs and TIMPs in acute myocardial infarction thrombi.
Main Methods:
- Histological classification of 120 thrombectomy materials from acute myocardial infarction patients into fresh, lytic, or organized thrombi.
- Immunostaining and polymerase chain reaction were used to determine the presence and cellular origin of specific MMPs (MMP-1, MMP-2, MMP-8, MMP-9, MMP-14) and TIMPs (TIMP-1, TIMP-2, TIMP-3).
Main Results:
- MMPs and TIMPs were detected in all thrombus samples, exhibiting distinct temporal changes.
- Early thrombus stages showed high MMP and TIMP production by neutrophilic granulocytes.
- Organizing thrombi exhibited decreased MMP-1, MMP-8, MMP-9, TIMP-2, and TIMP-3, while MMP-2 and MMP-14 remained consistently high.
Conclusions:
- A complex, time-dependent function of MMPs, primarily derived from granulocytes, is indicated in thrombus healing.
- Temporal changes in MMPs and TIMPs suggest a regulated process in thrombus evolution after plaque rupture.
- Specific MMPs and TIMPs show distinct patterns of expression and cellular origin throughout thrombus development.
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