Trial reportThrombosis and haemostasis2015
Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant.
Trial report in Thrombosis and haemostasis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 48 citations in OpenAlex.
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Article
- Broadly inhibitory antibodies against severe malaria virulence proteins.bioRxiv : the preprint server for biology · 2024Article
- Variable Surface Antigens ofProtein and peptide letters · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
- Binding of Plasmodium falciparum-Infected Red Blood Cells to Engineered 3D Microvessels.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Kinetics of monocyte subpopulations during experimental cerebral malaria and its resolution in a model of late chloroquine treatment.Frontiers in cellular and infection microbiology · 2022Article
- Article
- Determinants of brain swelling in pediatric and adult cerebral malaria.JCI insight · 2021Article
- Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes.PLoS pathogens · 2021Article
- Structure-Guided Design of a Synthetic Mimic of an Endothelial Protein C Receptor-Binding PfEMP1 Protein.mSphere · 2021Article
- Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria.Blood advances · 2020Article
- Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies.Malaria journal · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption.Scientific reports · 2019Article
- Activated protein C in neuroprotection and malaria.Current opinion in hematology · 2019Review
- Article
- Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.EMBO molecular medicine · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The Endothelial Protein C receptor (EPCR) is essential for the anticoagulant and cytoprotective functions of the Protein C (PC) system. Selected variants of the malaria parasite protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) associated with severe malaria, including cerebral malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRα1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR functions. CIDRα1.1 severely impaired endothelial PC activation and effectively blocked APC-mediated activation of protease-activated receptor-1 (PAR1) and associated barrier protective effects of APC on endothelial cells. A soluble EPCR variant (E86A-sEPCR) bound CIDRα1.1 with high affinity and did not interfere with (A)PC binding to cellular EPCR. E86A-sEPCR used as a decoy to capture PfEMP1, permitted normal PC activation on endothelial cells, normal barrier protective effects of APC, and greatly reduced cytoadhesion of infected erythrocytes to brain endothelial cells. These data imply important contributions of PfEMP1-induced protein C pathway defects in the pathogenesis of severe malaria. Furthermore, the E86A-sEPCR decoy provides a proof-of-principle strategy for the development of novel adjunct therapies for severe malaria.
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.