ArticleInternational journal of cardiology2015
Early matrix metalloproteinase-12 inhibition worsens post-myocardial infarction cardiac dysfunction by delaying inflammation resolution.
Article in International journal of cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Cardiac repair after myocardial infarction: A two-sided role of inflammation-mediated.Frontiers in cardiovascular medicine · 2022Pooled it
- Guidelines for in vivo mouse models of myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2021Guideline
- Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- Spatiotemporal Nanotherapy After Myocardial Infarction: Targeting the Inflammatory-to-reparative Transition With Extracellular Vesicles and Engineered Nanoparticles.Cardiovascular drugs and therapy · 2026Review
- Matrix metalloproteinases and risk of cardiovascular mortality and morbidity in the United Kingdom: A prospective cohort study with machine learning analysis.Preventive medicine reports · 2026Article
- A novel plasma proteomic signature predicts long-term incident heart failure risk among persons living with HIV.medRxiv : the preprint server for health sciences · 2026Article
- Plasma proteomics and incident coronary heart disease.Communications medicine · 2026Article
- Neutrophil death pathways in myocardial infarction: the balance between injury and repair.Frontiers in immunology · 2026Review
- Matrix metalloproteinase-12 in arterial diseases: context-dependent mechanisms of vascular remodeling and therapeutic implications.Frontiers in cardiovascular medicine · 2026Review
- Cross-Talk Between Neutrophils and Macrophages Post-Myocardial Infarction: From Inflammatory Drivers to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Matrix Metalloproteinases and Their Inhibitors in the Pathogenesis of Epithelial Differentiation, Vascular Disease, Endometriosis, and Ocular Fibrotic Pterygium.International journal of molecular sciences · 2025Review
- Mapping the knowledge of omics in myocardial infarction: A scientometric analysis in R Studio, VOSviewer, Citespace, and SciMAT.Medicine · 2025Article
- Unraveling the role of proteins in dementia: insights from two UK cohorts with causal evidence.Brain communications · 2025Article
- Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.International journal of molecular sciences · 2024Article
- Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Don't go breakin' my heart: cardioprotective alterations to the mechanical and structural properties of reperfused myocardium during post-infarction inflammation.Biophysical reviews · 2023Review
- Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.European heart journal · 2023Article
- Matrix metalloproteinases in coronary artery disease and myocardial infarction.Basic research in cardiology · 2023Review
- Homeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity.Circulation research · 2023Article
- The cardiac wound healing response to myocardial infarction.WIREs mechanisms of disease · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleMatrix metalloproteinases (MMPs) regulate remodeling of the left ventricle (LV) post-myocardial infarction (MI). MMP-12 has potent macrophage-dependent remodeling properties in the atherosclerotic plaque; however, post-MI roles have not been examined.
objectiveThe goal was to determine MMP-12 post-MI mechanisms. METHODS AND
resultsMale C57BL/6J mice (3-6 months old) were subjected to left coronary artery ligation. Saline or the RXP 470.1 MMP-12 inhibitor (MMP-12i; 0.5mg/kg/day) was delivered by osmotic mini-pump beginning 3h post-MI, and mice were sacrificed at day (d)1, 3, 5 or 7 post-MI and compared to d0 controls (mice without MI; n=6-12/group/time). MMP-12 expression increased early post-MI, and contrary to expected, neutrophils were a surprising early cellular source for MMP-12. MMP-12i reduced MMP-12 activity 33 ± 1% at d1 post-MI. Despite similar infarct areas and survival rates, MMP-12i led to greater LV dilation and worsened LV function. At d7 post-MI, MMP-12i prolonged pro-inflammatory cytokine upregulation (IL1r1, IL6ra, IL11, and Cxcr5) and decreased CD44 (both gene and protein levels). Hyaluronan (HA), a CD44 ligand, was elevated at d1 and d7 post-MI with MMP12i, as a result of decreased fragmentation. Because CD44-HA regulates neutrophil removal, apoptosis markers were evaluated. Caspase 3 increased, while cleaved caspase 3 levels decreased in MMP-12i group at d7 post-MI, indicating reduced neutrophil apoptosis. In isolated neutrophils, active MMP-12 directly stimulated CD44, caspase 3, and caspase 8 expression.
conclusionOur results reveal a novel protective mechanism for MMP-12 in neutrophil biology. Post-MI, MMP-12i impaired CD44-HA interactions to suppress neutrophil apoptosis and prolong inflammation, which worsened LV function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.