ArticleArteriosclerosis, thrombosis, and vascular biology2014
Mechanism of race-dependent platelet activation through the protease-activated receptor-4 and Gq signaling axis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 56 citations in OpenAlex.
- Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome: Analysis from the TRACER trial.Blood cells, molecules & diseases · 2018Trial
- Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial.Nagoya journal of medical science · 2018Trial
- Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants.Clinical pharmacology and therapeutics · 2026Article
- Association of Platelet Aggregation With Markers of Alzheimer Disease Pathology in Middle-Aged Participants of the Framingham Heart Study.Neurology · 2025Article
- Observational Analyses of Ex Vivo Native American Platelet Responses.International journal of molecular sciences · 2024Observational
- Ethnic Disparities in the Risk Factors, Morbidity, and Mortality of Cardiovascular Disease in People With Diabetes.Journal of the Endocrine Society · 2024Review
- Article
- Investigating the catalytic efficiency of C22-Fatty acids with LOX human isozymes and the platelet response of the C22-oxylipin products.Archives of biochemistry and biophysics · 2023Article
- Species Differences in Platelet Protease-Activated Receptors.International journal of molecular sciences · 2023Review
- Antiplatelet Resistance: A Review of Concepts, Mechanisms, and Implications for Management in Acute Ischemic Stroke and Transient Ischemic Attack.Stroke (Hoboken, N.J.) · 2023Review
- P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Hormones, age, and sex affect platelet responsiveness in vitro.Transfusion · 2022Article
- Neutrophil cathepsin G proteolysis of protease-activated receptor 4 generates a novel, functional tethered ligand.Blood advances · 2022Article
- Four-Week Supplementation of Water-Soluble Tomato Extract Attenuates Platelet Function in Chinese Healthy Middle-Aged and Older Individuals: A Randomized, Double-Blinded, and Crossover Clinical Trial.Frontiers in nutrition · 2022Article
- Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets.Clinical pharmacology and therapeutics · 2021Article
- Platelet reactivity in response to aspirin and ticagrelor in African-Americans and European-Americans.Journal of thrombosis and thrombolysis · 2021Article
- Analysis of theFrontiers in genetics · 2020Article
- Not all (N)SAID and done: Effects of nonsteroidal anti-inflammatory drugs and paracetamol intake on platelets.Research and practice in thrombosis and haemostasis · 2020Review
- The protease-activated receptor 4 Ala120Thr variant alters platelet responsiveness to low-dose thrombin and protease-activated receptor 4 desensitization, and is blocked by non-competitive P2YJournal of thrombosis and haemostasis : JTH · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveBlack individuals are at an increased risk of myocardial infarction and stroke, 2 vascular diseases with strong thrombotic components. Platelet activation is a key step in platelet clot formation leading to myocardial infarction and stroke, and recent work supports a racial difference in platelet aggregation through the thrombin protease-activated receptors (PARs). The underlying mechanism for this racial difference, however, has not been established. Determining where in the signaling cascade these racial differences emerge will aid in understanding why individuals of differing racial ancestry may possess an inherent difference in their responsiveness to antiplatelet therapies. APPROACH AND
resultsWashed human platelets from black volunteers were hyperaggregable in response to PAR4-mediated platelet stimulation compared with whites. Interestingly, the racial difference in PAR4-mediated platelet aggregation persisted in platelets treated ex vivo with aspirin and 2MeSAMP (2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate), suggesting that the racial difference is independent of secondary feedback. Furthermore, stimulation of platelets from black donors with PAR4-activating peptide showed a potentiated level of activation through the Gq pathway compared with platelets from white donors. Differences in signaling included increased Ca(2+) mobilization, Rap1 (Ras-related protein 1) activation, and integrin αIIbβ3 activation with no observed difference in platelet protein expression between the groups tested.
conclusionsOur study is the first to demonstrate that the Gq pathway is differentially regulated by race after PAR4 stimulation in human platelets. Furthermore, the racial difference in PAR4-mediated platelet aggregation persisted in the presence of cyclooxygenase and P2Y12 receptor dual inhibition, suggesting that current antiplatelet therapy may provide less protection to blacks than whites.
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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.