ArticleBlood2025
LRRC8 complexes are ATP release channels that regulate platelet activation and arterial thrombosis.
Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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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.
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Who cites it
7 citing papers in PubMed.
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026Review
- Endothelial LRRC8C Associates With LRRC8A and LRRC8B to Regulate Vascular Reactivity and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Deep eutectic solvents@enteric technology for orally delivering anticoagulant macromolecule drug.Acta pharmaceutica Sinica. B · 2026Article
- Review
- Endothelial LRRC8A mitigates pressure overload-induced cardiac hypertrophy by promoting coronary angiogenesis.Angiogenesis · 2025Article
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28 authors.
Funding
Abstract
abstractPlatelet shape and volume changes are early mechanical events contributing to platelet activation and thrombosis. Here, we identify single-nucleotide polymorphisms in leucine-rich repeat-containing 8 (LRRC8) protein subunits that form the volume-regulated anion channel (VRAC), which are independently associated with altered mean platelet volume. LRRC8A is required for functional VRAC in megakaryocytes (MKs) and regulates platelet volume; adhesion; and agonist-stimulated activation, aggregation, adenosine triphosphate (ATP) secretion, and calcium mobilization. MK-specific LRRC8A conditional knockout mice have reduced laser injury-induced cremaster arteriolar thrombus formation and prolonged FeCl3 induced carotid arterial thrombosis without prolonged bleeding times. Mechanistically, platelet LRRC8A mediates swell-induced cytosolic ATP release to amplify agonist-stimulated calcium-phosphoinositide 3-kinase-protein kinase B signaling. Small-molecule LRRC8 channel inhibitors recapitulate defects observed in LRRC8A-null platelets in vitro and in vivo. These studies identify the mechanoresponsive LRRC8 channel complex as an ATP release channel in platelets, which positively regulates platelet function and thrombosis, providing a proof of concept for a novel antithrombotic drug target.
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