ArticleProceedings of the National Academy of Sciences of the United States of America2018
PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment.EMBO molecular medicine · 2026Article
- Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?Bioengineering & translational medicine · 2026Review
- Protease-Activated Receptor 1 as an Endogenous Model of Peptidergic Gαq-Gα12-Biased G Protein Signaling.bioRxiv : the preprint server for biology · 2026Article
- Understanding how a highly prevalent GRK5 polymorphism affects platelets and enhances thrombotic risk.Blood · 2026Article
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- Protease-activated receptor 1 as an endogenous model of peptidergic Gαq-Gα12-biased G protein signaling.Frontiers in molecular biosciences · 2026Article
- Stanniocalcin2, A Promising New Target for Identifying Patients with Stroke/Ictus.International journal of molecular sciences · 2025Article
- Activated protein C ameliorates diabetes-induced atherosclerosis by sustaining macrophage efferocytosis.Cardiovascular diabetology · 2025Article
- Identification of novel gene expression programs in thrombin-stimulated hepatic stellate cells.Research and practice in thrombosis and haemostasis · 2025Article
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Wound Healing in Human Skin Equivalents Reconstructed with Biopolymers Under Fine-Dust Exposure.Polymers · 2025Article
- Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent.Bioactive materials · 2024Article
- Hepatocyte-independent PAR1-biased signaling controls liver pathology in experimental obesity.Journal of thrombosis and haemostasis : JTH · 2024Article
- Angiogenesis-Enabled Human Ovarian Tumor Microenvironment-Chip Evaluates Pathophysiology of Platelets in Microcirculation.Advanced healthcare materials · 2024Article
- Characterizing Modulators of Protease-activated Receptors with a Calcium Mobilization Assay Using a Plate Reader.Journal of visualized experiments : JoVE · 2024Article
- Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.Journal of cardiovascular translational research · 2024Review
- Sulfenylation links oxidative stress to protein disulfide isomerase oxidase activity and thrombus formation.Journal of thrombosis and haemostasis : JTH · 2023Article
- Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.Cell research · 2023Article
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB-mediated transcriptional activation and up-regulation of select cytoprotective transcripts.
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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.