Trial reportBlood2013
Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9.
Trial report in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 263 citations in OpenAlex.
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study.The American journal of clinical nutrition · 2023Trial
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Article
- Macrophage-derived fibronectin suppresses antitumor immunity via tissue stiffening and immunosuppressive cell induction in cancer mouse models.Nature communications · 2026Article
- Treatment with Sildenafil Promotes Angiogenesis and Modulates Immune Response in Ischemic Muscle Tissue.Current issues in molecular biology · 2026Article
- A nanosystem targeting tissue inhibitor of metalloproteinase-1 for continuous spatiotemporal idiopathic pulmonary fibrosis therapy.Nature communications · 2026Article
- Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.Journal of Cancer · 2026Review
- Reversing diabetic wound stagnation: macrophage polarization dysregulation as a therapeutic linchpin from pathogenesis to precision interventions.Burns & trauma · 2026Review
- Plasma Fibronectin Drives Macrophage Elongation via Integrin β3-Tie2 Axis in Blood Clots.Cancers · 2025Article
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- Selumetinib promotes coronary collateral circulation by inducing M2-like macrophage polarization following myocardial infarction.Acta pharmacologica Sinica · 2025Article
- Engineered small extracellular vesicles for targeted delivery of perlecan to stabilise the blood-spinal cord barrier after spinal cord injury.Clinical and translational medicine · 2025Article
- Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025Review
- Macrophage phenotypes modulate neoangiogenesis and fibroblast profiles in synovial-like organoid cultures.Osteoarthritis and cartilage · 2025Article
- Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.Dental materials : official publication of the Academy of Dental Materials · 2025Review
- 4-Octyl Itaconate Alleviates Myocardial Ischemia-Reperfusion Injury Through Promoting Angiogenesis via ERK Signaling Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophages as Multifaceted Orchestrators of Tissue Repair: Bridging Inflammation, Regeneration, and Therapeutic Innovation.Journal of inflammation research · 2025Review
- Identification and validation of key biomarkers of the glycolysis-ketone body metabolism in heart failure based on multi-omics and machine learning.Frontiers in cardiovascular medicine · 2025Article
- Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.Journal of biomedical materials research. Part A · 2025Article
92 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 1 institution in 1 country.
Funding
Abstract
A proangiogenic function of tissue-infiltrating monocytes/macrophages has long been attributed to their matrix metalloproteinase-9 zymogen (proMMP-9). Herein, we evaluated the capacity of human monocytes, mature M0 macrophages, and M1- and M2-polarized macrophages to induce proMMP-9-mediated angiogenesis. Only M2 macrophages induced angiogenesis at levels comparable with highly angiogenic neutrophils previously shown to release their proMMP-9 in a unique form, free of tissue inhibitor of metalloproteinases-1 (TIMP-1). Macrophage differentiation was accompanied by induction of low-angiogenic, TIMP-1-encumbered proMMP-9. However, polarization toward the M2, but not the M1 phenotype, caused a substantial downregulation of TIMP-1 expression, resulting in production of angiogenic, TIMP-deficient proMMP-9. Correspondingly, the angiogenic potency of M2 proMMP-9 was lost after its complexing with TIMP-1, whereas TIMP-1 silencing in M0/M1 macrophages rendered them both angiogenic. Similar to human cells, murine bone marrow-derived M2 macrophages also shut down their TIMP-1 expression and produced proMMP-9 unencumbered by TIMP-1. Providing proof that angiogenic capacity of murine M2 macrophages depended on their TIMP-free proMMP-9, Mmp9-null M2 macrophages were nonangiogenic, although their TIMP-1 was severely downregulated. Our study provides a unifying molecular mechanism for high angiogenic capacity of TIMP-free proMMP-9 that would be uniquely produced in a pathophysiological microenvironment by influxing neutrophils and/or M2 polarized macrophages.
Indexed as
Identifiers
What OpenQuestion holds
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.