ArticleEMBO molecular medicine2011
A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis.
Article in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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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.
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.
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Who cites it
71 citing papers in PubMed, 116 citations in OpenAlex.
- A double-blind, randomized, placebo-controlled pilot trial to evaluate safety and efficacy of vorapaxar on arteriovenous fistula maturation.The journal of vascular access · 2020Trial
- Neutrophil cathepsin G potentiates biased signaling through protease-activated receptor 4.Blood advances · 2026Article
- Prediction of Targets and Mechanisms of Top Ten Core "Food-Medicine Homologous Traditional Chinese Medicines" in Delaying Vascular Aging: An Integrative Computational Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- A systematic exploration of gut microbiota-driven blood metabolites in sepsis: an integrated bioinformatics and genetic association study.Frontiers in genetics · 2026Article
- Increased metallopeptidase activity, compromised endothelial integrity and impaired pathogen recognition revealed by transcriptomics inCurrent research in parasitology & vector-borne diseases · 2026Article
- From theory to platelets: unraveling the history and complexities of biased signaling.Blood vessels, thrombosis & hemostasis · 2025Review
- Biological attributes of zinc-dependent endopeptidases in endothelial dysfunction associated with sepsis: a narrative review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Clinical and Proteomic Insights into a Cytokine Release Syndrome Triggered by Tebentafusp in a Metastatic Uveal Melanoma Patient: Case Report.Journal of clinical medicine · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- The Relationship Between Acute Kidney Injury in Sepsis Patients and Coagulation Dysfunction and Prognosis.Open access emergency medicine : OAEM · 2024Article
- Review
- Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- The Role of Matrix Metalloproteinase in Inflammation with a Focus on Infectious Diseases.International journal of molecular sciences · 2022Review
- Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis.EBioMedicine · 2022Article
- The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.Kidney international supplements · 2022Review
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
- Intra-articular MMP-1 in the spinal facet joint induces sustained pain and neuronal dysregulation in the DRG and spinal cord, and alters ligament kinematics under tensile loading.Frontiers in bioengineering and biotechnology · 2022Article
- Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.Cell death discovery · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Sepsis is a deadly disease characterized by the inability to regulate the inflammatory-coagulation response in which the endothelium plays a key role. The cause of this perturbation remains poorly understood and has hampered the development of effective therapeutics. Matrix metalloproteases (MMPs) are involved in the host response to pathogens, but can also cause uncontrolled tissue damage and contribute to mortality. We found that human sepsis patients had markedly elevated plasma proMMP-1 and active MMP-1 levels, which correlated with death at 7 and 28 days after diagnosis. Likewise, septic mice had increased plasma levels of the MMP-1 ortholog, MMP-1a. We identified mouse MMP-1a as an agonist of protease-activated receptor-1 (PAR1) on endothelial cells. MMP-1a was released from endothelial cells in septic mice. Blockade of MMP-1 activity suppressed endothelial barrier disruption, disseminated intravascular coagulation (DIC), lung vascular permeability as well as the cytokine storm and improved survival, which was lost in PAR1-deficient mice. Infusion of human MMP-1 increased lung vascular permeability in normal wild-type mice but not in PAR1-deficient mice. These findings implicate MMP-1 as an important activator of PAR1 in sepsis and suggest that therapeutics that target MMP1-PAR1 may prove beneficial in the treatment of sepsis.
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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.