ReviewThrombosis and haemostasis2014
Cytoprotective-selective activated protein C therapy for ischaemic stroke.
Review in Thrombosis and haemostasis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 51 citations in OpenAlex.
- Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant.Thrombosis and haemostasis · 2015Trial
- Integrative proteogenomic analyses identify plasma proteins that impact the risk of ischemic stroke.Communications medicine · 2026Article
- Microcirculatory failure after successful recanalization in ischemic stroke: insights into mechanisms, imaging, and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Thrombomodulin-Induced Prevention of Peripheral Neuropathy in Oxaliplatin-Treated Mice Involves Complement C5a Inactivation and PAR1 Activation in Addition To HMGB1 Degradation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial.Communications medicine · 2024Article
- Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease.Blood advances · 2024Article
- 3K3A-Activated Protein C Protects the Blood-Brain Barrier and Neurons From Accelerated Ischemic Injury Caused by Pericyte Deficiency in Mice.Frontiers in neuroscience · 2022Article
- Long-term outcomes of intravitreal activated protein C injection for ischemic central retinal vein occlusion: an extension trial.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Cerebral Cavernous Malformation: From Mechanism to Therapy.Circulation research · 2021Review
- Stroke Treatment With PAR-1 Agents to Decrease Hemorrhagic Transformation.Frontiers in neurology · 2021Review
- Therapeutic strategies for thrombosis: new targets and approaches.Nature reviews. Drug discovery · 2020Review
- 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice.The Journal of experimental medicine · 2019Article
- Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice.Blood · 2019Article
- Review
- Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- Review
- α2-Macroglobulin Is a Significant In Vivo Inhibitor of Activated Protein C and Low APC:α2M Levels Are Associated with Venous Thromboembolism.Thrombosis and haemostasis · 2018Article
- Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2018Article
- Neuro-Immune Hemostasis: Homeostasis and Diseases in the Central Nervous System.Frontiers in cellular neuroscience · 2018Review
- Endothelial microparticles released by activated protein C protect beta cells through EPCR/PAR1 and annexin A1/FPR2 pathways in islets.Journal of cellular and molecular medicine · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Despite years of research and efforts to translate stroke research to clinical therapy, ischaemic stroke remains a major cause of death, disability, and diminished quality of life. Primary and secondary preventive measures combined with improved quality of care have made significant progress. However, no novel drug for ischaemic stroke therapy has been approved in the past decade. Numerous studies have shown beneficial effects of activated protein C (APC) in rodent stroke models. In addition to its natural anticoagulant functions, APC conveys multiple direct cytoprotective effects on many different cell types that involve multiple receptors including protease activated receptor (PAR) 1, PAR3, and the endothelial protein C receptor (EPCR). Application of molecular engineered APC variants with altered selectivity profiles to rodent stroke models demonstrated that the beneficial effects of APC primarily require its cytoprotective activities but not its anticoagulant activities. Extensive basic, preclinical, and clinical research provided a compelling rationale based on strong evidence for translation of APC therapy that has led to the clinical development of the cytoprotective-selective APC variant, 3K3A-APC, for ischaemic stroke. Recent identification of non-canonical PAR1 and PAR3 activation by APC that give rise to novel tethered-ligands capable of inducing biased cytoprotective signalling as opposed to the canonical signalling provides a mechanistic explanation for how APC-mediated PAR activation can selectively induce cytoprotective signalling pathways. Collectively, these paradigm-shifting discoveries provide detailed insights into the receptor targets and the molecular mechanisms for neuroprotection by cytoprotective-selective 3K3A-APC, which is currently a biologic drug in clinical trials for ischaemic stroke.
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.