ArticleArteriosclerosis, thrombosis, and vascular biology2008
Low tissue inhibitor of metalloproteinases 3 and high matrix metalloproteinase 14 levels defines a subpopulation of highly invasive foam-cell macrophages.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- Interleukin-16 upregulates tissue inhibitor of metalloproteinase 3 to promote atherosclerotic plaque stability.Journal of translational medicine · 2026Article
- Epigenetic regulation of TIMP-3 expression in human macrophages via physiological and pharmacological modification of histone3 lysine27 (H3K27).Molecular biology reports · 2025Article
- Unveiling TIMPs: A Systematic Review of Their Role as Biomarkers in Atherosclerosis and Coronary Artery Disease.Diseases (Basel, Switzerland) · 2024Review
- Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2021Review
- Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis.Nature communications · 2021Article
- ADAMTS proteases in cardiovascular physiology and disease.Open biology · 2020Review
- Galectin-3 Identifies a Subset of Macrophages With a Potential Beneficial Role in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Foam Cells: One Size Doesn't Fit All.Trends in immunology · 2019Review
- MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin.Circulation research · 2017Article
- Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion.Cardiovascular research · 2016Article
- Article
- Transient collagen triple helix binding to a key metalloproteinase in invasion and development.Structure (London, England : 1993) · 2015Article
- A model to explain specific cellular communications and cellular harmony:- a hypothesis of coupled cells and interactive coupling molecules.Theoretical biology & medical modelling · 2014Article
- Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability.Mediators of inflammation · 2014Article
- Tissue inhibitor of metalloproteinases-3 moderates the proinflammatory status of macrophages.American journal of respiratory cell and molecular biology · 2013Article
- Novel proteolytic microvesicles released from human macrophages after exposure to tobacco smoke.The American journal of pathology · 2013Article
- Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.PloS one · 2013Article
- Proprotein convertase subtilisin/kexin type 3 promotes adipose tissue-driven macrophage chemotaxis and is increased in obesity.PloS one · 2013Article
- Pivotal roles of monocytes/macrophages in stroke.Mediators of inflammation · 2013Review
- Carotid atherosclerotic plaque matrix metalloproteinase-12-positive macrophage subpopulation predicts adverse outcome after endarterectomy.Journal of the American Heart Association · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAn excess of metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs) may favor atherosclerotic plaque rupture. We compared TIMP levels in nonfoamy and foam-cell macrophages (FCM) generated in vivo. METHODS AND
resultsIn vivo generated rabbit FCM exhibited 84% reduced TIMP-3 protein compared to nonfoamy macrophages, and immunocytochemistry revealed a TIMP-3 negative subset (28%). Strikingly, only TIMP-3 negative FCM invaded a synthetic basement membrane, and invasion was inhibited by exogenous TIMP-3. TIMP-3 negative FCM also had increased proliferation and apoptosis rates compared to TIMP-3 positive cells, which were retarded by exogenous TIMP-3; this also reduced gelatinolytic activity. TIMP-3 negative FCM were found at the base of advanced rabbit plaques and in the rupture-prone shoulders of human plaques. To explain the actions of low TIMP-3 we observed a 26-fold increase in MT1-MMP (MMP-14) protein in FCM. Adding an MT1-MMP neutralizing antibody reduced foam-cell invasion, apoptosis, and gelatinolytic activity. Furthermore, MT1-MMP overexpressing and TIMP-3 negative FCM were found at the same locations in atherosclerotic plaques.
conclusionsThese results demonstrate that TIMP-3 is downregulated in a distinct subpopulation of FCM which have increased MMP-14. These cells are highly invasive and have increased proliferation and apoptosis, all properties expected to destabilise atherosclerotic plaques.
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