ArticleThe Journal of biological chemistry2013
Mitochondrially mediated integrin αIIbβ3 protein inactivation limits thrombus growth.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
The trial behind it
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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- The Mitochondrial Permeability Transition Pore in Platelets: Mechanisms, Physiological Roles, and Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets.International journal of molecular sciences · 2024Article
- Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge.International journal of molecular sciences · 2022Review
- Genetic deletion of p66shc and/or cyclophilin D results in decreased pulmonary vascular tone.Cardiovascular research · 2022Article
- Opposing Roles of GSK3α and GSK3β Phosphorylation in Platelet Function and Thrombosis.International journal of molecular sciences · 2021Article
- COVID-19 patients exhibit reduced procoagulant platelet responses.Journal of thrombosis and haemostasis : JTH · 2020Article
- Article
- Peripheral Blood Mononuclear Cells and Platelets Mitochondrial Dysfunction, Oxidative Stress, and Circulating mtDNA in Cardiovascular Diseases.Journal of clinical medicine · 2020Review
- Linagliptin Regulates the Mitochondrial Respiratory Reserve to Alter Platelet Activation and Arterial Thrombosis.Frontiers in pharmacology · 2020Article
- CD36 and ERK5 link dyslipidemia to apoptotic-like platelet procoagulant function.Current opinion in hematology · 2019Review
- Functional cyclophilin D moderates platelet adhesion, but enhances the lytic resistance of fibrin.Scientific reports · 2018Article
- Regulatory role of calpain in neuronal death.Neural regeneration research · 2018Review
- Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis.Circulation research · 2018Review
- Oxidative stress induced modulation of platelet integrin α2bβ3 expression and shedding may predict the risk of major bleeding in heart failure patients supported by continuous flow left ventricular assist devices.Thrombosis research · 2017Article
- Inner Mitochondrial Membrane Disruption Links Apoptotic and Agonist-Initiated Phosphatidylserine Externalization in Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Article
- IL-17 Induces MPTP opening through ERK2 and P53 signaling pathway in human platelets.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2015Article
- Microvesicles from platelets: novel drivers of vascular inflammation.Thrombosis and haemostasis · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
When platelets are strongly stimulated, a procoagulant platelet subpopulation is formed that is characterized by phosphatidylserine (PS) exposure and epitope modulation of integrin αIIbβ3 or a loss of binding of activation-dependent antibodies. Mitochondrial permeability transition pore (mPTP) formation, which is essential for the formation of procoagulant platelets, is impaired in the absence of cyclophilin D (CypD). Here we investigate the mechanisms responsible for these procoagulant platelet-associated changes in integrin αIIbβ3 and the physiologic role of procoagulant platelet formation in the regulation of platelet aggregation. Among strongly stimulated adherent platelets, integrin αIIbβ3 epitope changes, mPTP formation, PS exposure, and platelet rounding were closely associated. Furthermore, platelet mPTP formation resulted in a decreased ability to recruit additional platelets. In the absence of CypD, integrin αIIbβ3 function was accentuated in both static and flow conditions, and, in vivo, a prothrombotic phenotype occurred in mice with a platelet-specific deficiency of CypD. CypD-dependent proteolytic events, including cleavage of the integrin β3 cytoplasmic domain, coincided closely with integrin αIIbβ3 inactivation. Calpain inhibition blocked integrin β3 cleavage and inactivation but not mPTP formation or PS exposure, indicating that integrin inactivation and PS exposure are mediated by distinct pathways subsequent to mPTP formation. mPTP-dependent alkalinization occurred in procoagulant platelets, suggesting a possible alternative mechanism for enhancement of calpain activity in procoagulant platelets. Together, these results indicate that, in strongly stimulated platelets, mPTP formation initiates the calpain-dependent cleavage of integrin β3 and associated regulatory proteins, resulting in integrin αIIbβ3 inactivation, and demonstrate a novel CypD-dependent negative feedback mechanism that limits platelet aggregation and thrombotic occlusion.
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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.