ArticleThe Journal of clinical investigation2023
Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 34 citations in OpenAlex.
- Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.Arteriosclerosis, thrombosis, and vascular biology · 2023Trial
- Protein kinase WEE1 promotes cardiomyocytes ferroptosis and cardiac hypertrophy via the NF-κB/LCN2 axis.Acta pharmacologica Sinica · 2026Article
- Cardiac proteomic and phosphoproteomic profiling defines clinically relevant molecular subgroups in human heart failure.Nature cardiovascular research · 2026Article
- Phosphoproteomics in Vascular Biology and Disease: Illuminating Signaling in the Vessel.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Article
- Plasma exosomal hsa-miR-339-5p is associated with NOD-like receptor family CARD domain-containing 5 in heart failure with reduced ejection fraction.Scientific reports · 2026Article
- Article
- Transportation Noise and Cardiovascular Health: Evidence, Mechanisms, and Policy Imperatives.Anatolian journal of cardiology · 2025Review
- Cilostazol alleviates imatinib-induced myocardial injury in rats by modulating the TGF-β1/MAPK, SHC/Grb2/SOS signaling pathways and upregulating miRNA-195-5P.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- MAPK, PI3K/Akt Pathways, and GSK-3β Activity in Severe Acute Heart Failure in Intensive Care Patients: An Updated Review.Journal of cardiovascular development and disease · 2025Review
- The Role of the MAPK Signaling Pathway in Cardiovascular Disease: Pathophysiological Mechanisms and Clinical Therapy.International journal of molecular sciences · 2025Review
- Miglustat ameliorates isoproterenol-induced cardiac fibrosis via targeting UGCG.Molecular medicine (Cambridge, Mass.) · 2025Article
- Honey-fried licorice decoction ameliorates atrial fibrillation susceptibility by inhibiting the NOX2-ROS-TGF-β1 pathway.Frontiers in pharmacology · 2025Article
- Exploring molecular characteristics and interactions of blood stasis syndrome in ischemic heart failure by integrated multi-omics.Frontiers in molecular biosciences · 2025Article
- Multidisciplinary strategies to reduce radiotherapy-induced cardiotoxicity in breast cancer: surgical and technological innovations.Frontiers in oncology · 2025Review
- Uncovering Druggable Targets in Aortic Dissection: An Association Study Integrating Mendelian Randomization, pQTL, and Protein-Protein Interaction Network.Biomedicines · 2024Article
- Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.Research and practice in thrombosis and haemostasis · 2024Article
- Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.Blood · 2024Article
- Article
- IdentifyingBiomolecules · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify a profibrotic coagulation signaling pathway that can be targeted for improved cardiac function following MI with persistent ischemia. Quantitative phosphoproteomics of cardiac tissue revealed an upregulated mitogen-activated protein kinase (MAPK) pathway in human IHF. Intervention in this pathway with trametinib improves myocardial function and prevents fibrotic remodeling in a murine model of non-reperfused MI. MAPK activation in MI requires myeloid cell signaling of protease-activated receptor 2 linked to the cytoplasmic domain of the coagulation initiator tissue factor (TF). They act upstream of pro-oxidant NOX2 NADPH oxidase, ERK1/2 phosphorylation, and activation of profibrotic TGF-β1. Specific targeting with the TF inhibitor nematode anticoagulant protein c2 (NAPc2) starting 1 day after established experimental MI averts IHF. Increased TF cytoplasmic domain phosphorylation in circulating monocytes from patients with subacute MI identifies a potential thromboinflammatory biomarker reflective of increased risk for IHF and suitable for patient selection to receive targeted TF inhibition therapy.
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.