ArticleThe Journal of clinical investigation2016
Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 75 citations in OpenAlex.
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Plasmodium-induced disruption of brain endothelial barrier integrity in vitro and in mice is prevented by inhibitors of farnesyltransferase.Malaria journal · 2026Article
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- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
- Investigating angiotensin II concentration in modulatingFrontiers in parasitology · 2026Article
- Proteasomal inhibition compromises microvascular integrity via distinct effects on non-immune endothelial cells and immune cells.Frontiers in immunology · 2026Article
- Revisiting renin-angiotensin-aldosterone system in aging: translational insights from bench to bedside and back.The Journal of clinical investigation · 2025Review
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Febrile temperature enhancesbioRxiv : the preprint server for biology · 2025Article
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Polycyclitol Derivatives Restore Long- Term Memory Via cdk5/p25 Activation of Tau Signaling in Experimental Cerebral Malaria.Neurochemical research · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Differential restriction of chikungunya virus in primary human cardiac endothelial cells occurs at multiple steps in the viral life cycle.PLoS neglected tropical diseases · 2025Article
- Differential restriction of chikungunya virus in primary human cardiac endothelial cells occurs at multiple steps in the viral life cycle.bioRxiv : the preprint server for biology · 2024Article
- Synthetic angiotensin II peptide derivatives confer protection against cerebral and severe non-cerebral malaria in murine models.Scientific reports · 2024Article
- Hypertension Increases Susceptibility to Experimental Malaria in Mice.Function (Oxford, England) · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.JCI insight · 2023Article
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum-infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter-endothelial cell junctions in human brain microvascular endothelial cells (HBMECs). Inhibition of β-catenin-induced TCF/LEF transcription in the nucleus of HBMECs prevented the disruption of endothelial junctions, confirming that β-catenin is a key mediator of P. falciparum adverse effects on endothelial integrity. Blockade of the angiotensin II type 1 receptor (AT1) or stimulation of the type 2 receptor (AT2) abrogated Pf-iRBC-induced activation of β-catenin and prevented the disruption of HBMEC monolayers. In a mouse model of cerebral malaria, modulation of angiotensin II receptors produced similar effects, leading to protection against cerebral malaria, reduced cerebral hemorrhages, and increased survival. In contrast, AT2-deficient mice were more susceptible to cerebral malaria. The interrelation of the β-catenin and the angiotensin II signaling pathways opens immediate host-targeted therapeutic possibilities for cerebral malaria and other diseases in which brain endothelial integrity is compromised.
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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.