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Record W2888862173 · doi:10.1038/s41467-018-05806-0

Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis

2018· article· en· W2888862173 on OpenAlexafffund
Xiaohong Xu, Yiming Wang, Reheman Adili, Lining Arnold Ju, Christopher M. Spring, Joseph W. Jin, Miguel A. D. Neves, Pingguo Chen, Yan Yang, Xi Lei, Yunfeng Chen, Reid C. Gallant, Miao Xu, Hailong Zhang, Jina Song, Peifeng Ke, Dan Zhang, Naadiya Carrim, Siyang Yu, Guangheng Zhu, Yi‐Min She, Terry D. Cyr, Wenbin Fu, Guoqing Liu, Philip W. Connelly, Margaret L. Rand, Khosrow Adeli, John Freedman, Jeffrey E. Lee, Patrick Tso, Patrizia Marchese, W. Sean Davidson, Shaun P. Jackson, Cheng Zhu, Zaverio M. Ruggeri, Heyu Ni

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldMedicine
TopicPlatelet Disorders and Treatments
Canadian institutionsHospital for Sick ChildrenHealth CanadaCanadian Blood ServicesUniversity of TorontoSt. Michael's Hospital
FundersSydney Medical SchoolCanadian Institutes of Health ResearchNational Institutes of HealthCardiac Society of Australia and New ZealandDiabetes AustraliaCanadian Blood ServicesNational Heart Foundation of AustraliaRoyal College of Pathologists of AustralasiaNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteHeart and Stroke Foundation of Canada
KeywordsIntegrinPlateletHemostasisPlatelet activationChemistryApolipoprotein BPostprandialInternal medicineBiochemistryCell biologyEndocrinologyPharmacologyMedicineReceptorBiologyCholesterolInsulin

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.389
Threshold uncertainty score0.384

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.337
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations113
Published2018
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicPlatelet Disorders and TreatmentsFrench-language works237,207