ArticleNature communications2018
Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
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68citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 2% of its field
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The trial behind it
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Genetic architecture and cross-platform validation of apolipoprotein A-IV concentrations.Genome biology · 2026Pooled it
- The high-density lipoprotein lipidome in metabolic syndrome: A systematic review.European journal of clinical investigation · 2026Pooled it
- Dose-dependent effects of anthocyanin supplementation on platelet function in subjects with dyslipidemia: A randomized clinical trial.EBioMedicine · 2021Trial
- In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.Scientific reports · 2021Trial
- Plasma cell-free RNA ITGB3 is associated with long-term clinical benefit in patients with non-small cell lung cancer receiving immunochemotherapy.Journal for immunotherapy of cancer · 2026Article
- Profiling Cardiovascular Disease-Associated Changes in the Composition of High-Density Lipoprotein Particles.Cardiovascular drugs and therapy · 2026Review
- Plasma apolipoprotein A-IV deficiency as a proteomics-identified diagnostic biomarker for heat stroke: A prospective 2-center study.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Article
- Biology of HDL: From Structural Heterogeneity to Dysfunctional Remodeling in Cardiovascular Disease and Comorbidities.Antioxidants (Basel, Switzerland) · 2026Review
- Effects of transcutaneous auricular vagus nerve stimulation or combined vagal and trigeminal nerve stimulation on platelet function and laboratory hemostasis parameters in healthy human subjects.Bioelectronic medicine · 2026Article
- Platelet CLEC-2 activation leads to GPIb⍺ shedding: Implications for doxorubicin chemotherapy and thrombosis.The Journal of biological chemistry · 2026Article
- The Plasma Glycoprotein Milieu in the Hemato-Oncological Patient Inhibits Platelet Function.Biomolecules · 2026Article
- Elevated levels of apolipoprotein C3 impair platelet function and reduce thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Article
- Obesity disrupts ovarian hemodynamics during the preovulatory and luteal phases in mice†.Biology of reproduction · 2026Article
- HDL in Abdominal Aortic Aneurysm: Mechanistic Insight and Therapeutic Potential.Current atherosclerosis reports · 2026Review
- Dynamic Force Spectroscopy for Analysis of Multiple Disulfide-Bonded Protein States.Methods in molecular biology (Clifton, N.J.) · 2026Article
- An overview of mechanical microenvironment and mechanotransduction in intervertebral disc degeneration.Experimental & molecular medicine · 2025Review
- Article
- Article
- Apolipoprotein A (ApoA) in Neurological Disorders: Connections and Insights.International journal of molecular sciences · 2025Review
- Apolipoprotein-A1 transports and regulates MMP2 in the blood.Nature communications · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
37 authors at 9 institutions in 4 countries.
Xiaohong Ruby XuDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Yiming WangDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Reheman AdiliDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Lining JuCoulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA, 30332.ORCID http://orcid.org/0000-0002-7591-0864
Christopher M SpringDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Joseph Wuxun JinDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Hong YangDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Miguel A D NevesDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Pingguo ChenDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Yan YangDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Xi LeiDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Yunfeng ChenPetit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA, 30332.
Reid C GallantDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Miao XuDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Hailong ZhangDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Jina SongDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Peifeng KeGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China, 510000.
Dan ZhangDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Naadiya CarrimDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Si-Yang YuDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Guangheng ZhuDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, Canada, M5B 1W8.
Yi-Min SheCentre for Biologics Research, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada, K1A 0M2.
Terry CyrCentre for Biologics Research, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada, K1A 0M2.
Wenbin FuDepartment of Acupuncture and Moxibustion, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China, 510120.
Guoqing LiuInstitute of Cardiovascular Science, Peking University Health Science Center, Beijing, P.R. China, 100083.
Philip W ConnellyDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Margaret L RandDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Khosrow AdeliDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
John FreedmanDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Jeffrey E LeeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1.
Patrick TsoDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA, 45219.
Patrizia MarcheseDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA, 92037.
W Sean DavidsonDepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA, 45219.
Shaun P JacksonHeart Research Institute, and Charles Perkins Centre, The University of Sydney, Camperdown, Australia, 2006.
Cheng ZhuCoulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA, 30332.ORCID http://orcid.org/0000-0002-1718-565X
Zaverio M RuggeriDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA, 92037.ORCID http://orcid.org/0000-0003-0807-1295
Heyu NiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, M5S 1A1. nih@smh.ca.
St. Michael's Hospital · CAGuangzhou University of Chinese Medicine · CNScripps Research Institute · USUniversity of Toronto · CAGeorgia Institute of Technology · USHealth Canada · CAUniversity of Cincinnati · USPeking University · CNThe University of Sydney · AU
Funding
THROMBUS FORMATION IN BABOONSP01HL031950 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 1985 to 2015
$29.4MLipid profile, lipoprotein and apolipoprotein composition, and intestinal fat absorption efficiency in germ-free and conventional miceU2CDK059630 · NIDDK · UNIVERSITY OF CINCINNATI · PI LIU, MIN · 2016 to 2021
$4.9MSingle-platelet analysis of mechano-reception by GPIb alphaR01HL132019 · NHLBI · GEORGIA INSTITUTE OF TECHNOLOGY · PI ZHU, CHENG · 2016 to 2024
$3.8MRole of the GI lymphatic system in hormonal signaling and nutrient metabolismR01DK119135 · NIDDK · UNIVERSITY OF CINCINNATI · PI LIU, MIN, TSO, PATRICK · 2018 to 2022
$3.0MApolipoprotein AV and intestinal transportR01DK103557 · NIDDK · UNIVERSITY OF CINCINNATI · PI TSO, PATRICK · 2015 to 2019
$1.9MNHLBI NIH HHS P01 HL031950NHLBI NIH HHS R01 HL132019NIDDK NIH HHS R01 DK103557NIDDK NIH HHS R01 DK119135NIDDK NIH HHS U2C DK059630
Abstract
Platelet αIIbβ3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbβ3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.
Indexed as
AdultAnimalsApolipoproteins AAspartic AcidBinding SitesCircadian RhythmDisease Models, AnimalHumansMice, Inbred C57BLMice, TransgenicPlatelet AggregationPlatelet Aggregation InhibitorsPlatelet Glycoprotein GPIIb-IIIa ComplexPostprandial PeriodRecombinant ProteinsThrombosisapolipoprotein A-IVApolipoproteins AAspartic AcidPlatelet Aggregation InhibitorsPlatelet Glycoprotein GPIIb-IIIa ComplexRecombinant Proteins
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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.