Intercellular calcium communication regulates platelet aggregation and thrombus growth

The ability of platelets to form stable adhesion contacts with other activated platelets (platelet cohesion or aggregation) at sites of vascular injury is essential for hemostasis and thrombosis. In this study, we have examined the mechanisms regulating cytosolic calcium flux during the development of platelet–platelet adhesion contacts under the influence of flow. An examination of platelet calcium flux during platelet aggregate formation in vitro demonstrated a key role for intercellular calcium communication (ICC) in regulating the recruitment of translocating platelets into developing aggregates. We demonstrate that ICC is primarily mediated by a signaling mechanism operating between integrin αIIbβ3 and the recently cloned ADP purinergic receptor P2Y12. Furthermore, we demonstrate that the efficiency by which calcium signals are propagated within platelet aggregates plays an important role in dictating the rate and extent of thrombus growth.

• Publication year

  2003

• Venue

  Journal of Cell Biology

• Publication date

  2003-03-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200207119PMID 12668663PMCID 2172771
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Distinct glycoprotein Ib/V/IX and integrin alpha IIbbeta 3-dependent calcium signals cooperatively regulate platelet adhesion under flow.

  2002cited by this paper
• Distinct Glycoprotein Ib/V/IX and Integrin αIIbβ3-dependent Calcium Signals Cooperatively Regulate Platelet Adhesion under Flow*

  2002influential reference
• ATP induces Ca(2+) signaling in human chondrons cultured in three-dimensional agarose films.

  2001influential reference
• Effects of cAMP on intercellular coupling and osteoblast differentiation.

  2001cited by this paper
• Platelet Collagen Receptors

  2001cited by this paper
• Gap junctions and fluid flow response in MC3T3-E1 cells.

  2001cited by this paper
• Expression of Tissue Factor in High-Grade Carotid Artery Stenosis: Association With Plaque Destabilization

  2001cited by this paper
• Mechanism of intracellular Ca(2+)-wave propagation elicited by mechanical stimulation in cultured endothelial CPAE cells.

  2001cited by this paper
• Intercellular communication upon mechanical stimulation of CPAE- endothelial cells is mediated by nucleotides.

  2001cited by this paper
• Ca2+ signaling regulated by an ATP-dependent autocrine mechanism in astrocytes

  2001cited by this paper
• ADP Receptors of Platelets and their Inhibition

  2001cited by this paper
• ATP Mediates Calcium Signaling Between Astrocytes and Microglial Cells: Modulation by IFN-γ1

  2001cited by this paper
• Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice

  2001cited by this paper
• Fibrinogen binding to the integrin alpha(IIb)beta(3) modulates store-mediated calcium entry in human platelets.

  2001cited by this paper
• Role of von Willebrand factor in platelet thrombus formation.

  2000influential reference
• Synergistic adhesive interactions and signaling mechanisms operating between platelet glycoprotein Ib/IX and integrin alpha IIbbeta 3. Studies in human platelets ans transfected Chinese hamster ovary cells.

  2000influential reference
• P2Y1 Purinoceptor-Mediated Ca2+ Signaling and Ca2+ Wave Propagation in Dorsal Spinal Cord Astrocytes

  2000cited by this paper
• Synergistic Adhesive Interactions and Signaling Mechanisms Operating between Platelet Glycoprotein Ib/IX and Integrin αIIbβ3

  2000influential reference
• A revised model of platelet aggregation.

  2000influential reference
• Activity-Dependent Neuronal Control of Gap-Junctional Communication in Astrocytes

  2000influential reference
• Components of astrocytic intercellular calcium signaling

  2000cited by this paper
• High dose therapy and autologous hematopoietic stem cell transplantation in poor risk solid tumors of childhood.

  2000cited by this paper
• Interleukin‐1β Increases the Functional Expression of Connexin 43 in Articular Chondrocytes: Evidence for a Ca2+‐Dependent Mechanism

  2000cited by this paper
• Human Osteoblastic Cells Propagate Intercellular Calcium Signals by Two Different Mechanisms

  2000influential reference
• [Intra- and intercellular Ca(2+)-signal transduction].

  2000cited by this paper
• Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen.

  2000influential reference
• Real-time analysis of mural thrombus formation in various platelet aggregation disorders: distinct shear-dependent roles of platelet receptors and adhesive proteins under flow.

  1999cited by this paper
• Intra‐ and intercellular Ca2+ signaling in retinal pigment epithelial cells during mechanical stimulation

  1999cited by this paper
• Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

  1999cited by this paper
• Cytosolic calcium changes in a process of platelet adhesion and cohesion on a von Willebrand factor-coated surface under flow conditions

  1999cited by this paper
• Identification of Domains Responsible for von Willebrand Factor Type VI Collagen Interaction Mediating Platelet Adhesion under High Flow*

  1999influential reference
• ATP Released from Astrocytes Mediates Glial Calcium Waves

  1999influential reference
• TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs.

  1999cited by this paper
• Glycoprotein (GP) Ib-IX-transfected Cells Roll on a von Willebrand Factor Matrix under Flow

  1999cited by this paper
• Cytosolic calcium changes in a process of platelet adhesion and cohesion on a von Willebrand factor-coated surface under flow conditions.

  1999cited by this paper
• HEMOSTASIS , THROMBOSIS , AND VASCULAR BIOLOGY Contribution of Distinct Adhesive Interactions to Platelet Aggregation in Flowing Blood

  1999influential reference
• TNFα plus IFNγ induce the production of Alzheimer β‐amyloid peptides and decrease the secretion of APPs

  1999cited by this paper
• A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis.

  1998cited by this paper
• Roles of Ca2+, inositol trisphosphate and cyclic ADP-ribose in mediating intercellular Ca2+ signaling in sheep lens cells.

  1998cited by this paper
• Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions.

  1998influential reference
• Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.

  1998cited by this paper
• Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.

  1997cited by this paper
• Calpain Regulation of Cytoskeletal Signaling Complexes in Von Willebrand Factor-stimulated Platelets

  1997influential reference
• Identification of competitive antagonists of the P2Y1 receptor.

  1996cited by this paper
• Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor.

  1996influential reference
• [Platelet collagen receptors].

  1995cited by this paper
• Protein Tyrosine Phosphorylation in Human Platelets during Shear Stress-Induced Platelet Aggregation (SIPA) Is Regulated by Glycoprotein (GP) Ib/IX as well as GP IIb/IIIa and Requires Intact Cytoskeleton and Endogenous ADP

  1995cited by this paper
• Increased platelet deposition on atherosclerotic coronary arteries.

  1994influential reference
• Mechanisms of Shear-induced Platelet Adhesion and Aggregation

  1993cited by this paper
• A simplified method for culture of endothelial cells and analysis of adhesion of blood cells under conditions of flow.

  1993cited by this paper
• Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation.

  1992cited by this paper
• The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

  1991cited by this paper
• Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions.

  1989cited by this paper
• Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.

  1989cited by this paper
• Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.

  1989cited by this paper
• Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.

  1988cited by this paper
• Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa.

  1987cited by this paper
• Mechanisms of unstable angina.

  1986cited by this paper
• Platelet responses and metabolism

  1986cited by this paper
• Role of cytoplasmic and releasable ADP in platelet aggregation induced by laminar shear stress.

  1983cited by this paper
• von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease.

  1978cited by this paper
• Platelet Interaction with Collagen Fibrils in Flowing Blood

  1977cited by this paper
• Platelet Interaction with Collagen Fibrils in Flowing Blood

  1977influential reference
• Aggregation of Blood Platelets by Adenosine Diphosphate and its Reversal

  1962cited by this paper
• Immunochemical Studies on Human Siderophilin: Enzymatic Splitting of the Antigenic Structure of Siderophilin

  1962cited by this paper
• Studies on apyrases.

  1961cited by this paper

• Toll-like Receptor 7 Deficiency Attenuates Platelet Dysfunction in Sepsis

  2025cites this paper
• Green synthesis of Ce3+ doped V2O5 NPs as an advanced electrode material for possible supercapacitor and therapeutic applications

  2025cites this paper
• Transformative Eu3+ doped CoFe2O4 nanoparticles: A next-generation approach to high-performance energy storage, photocatalysis, and therapeutic applications

  2025cites this paper
• Sprayable, crosslinker-free, and in situ-forming Schiff-based hydrogels based on oxidized sodium alginate and carbohydrazide-modified gelatin for rapid hemostasis.

  2025cites this paper
• Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets

  2024cites this paper
• Ablation of CD38 Alleviates the Secondary Aggregation of Platelets

  2024cites this paper
• Embryos assist morphogenesis of others through calcium and ATP signaling mechanisms in collective teratogen resistance

  2024cites this paper
• Association between O-GlcNAc levels and platelet function in obese insulin-resistant subjects

  2024cites this paper
• Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke

  2024cites this paper
• Altered dynamics of calcium fluxes and mitochondrial metabolism in platelet activation-related disease and aging.

  2024cites this paper
• Hemostatic Dressing Immobilized with ε‐poly‐L‐lysine and Alginate Coated Mesoporous Bioactive Glass Prevents Blood Permeation by Pseudo‐Dewetting Behavior

  2024cites this paper
• Intraplatelet Calcium Signaling Regulates Thrombus Growth under Flow: Insights from a Multiscale Model

  2024cites this paper
• Beta-Sitosterol: A Comprehensive Review of Occurrence in Plants and its Therapeutic Potential in Treatment of Cardiovascular Disorders

  2024cites this paper
• Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism

  2023cites this paper
• Sodium bicarbonate as a local adjunctive agent for limiting platelet activation, aggregation, and adhesion within cardiovascular therapeutic devices

  2023cites this paper
• Mitochondrial calcium uniporter b deletion inhibits platelet function and reduces susceptibility to arterial thrombosis.

  2023cites this paper
• Research Progress on the Correlation between Blood Calcium and Hemorrhagic Progression and Neurological Prognosis in Traumatic Brain Injury

  2023cites this paper
• A microfluidic method to investigate platelet mechanotransduction under extensional strain

  2023cites this paper
• Platelets: Physiology and Biochemistry

  2023cites this paper
• Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations

  2023cites this paper
• Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy

  2022cites this paper
• Platelet procoagulant membrane dynamics: a key distinction between thrombosis and hemostasis?

  2022cites this paper
• Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment

  2022cites this paper
• Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study

  2022cites this paper
• A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death

  2022cites this paper
• Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders

  2021cites this paper
• Respective roles of Glycoprotein VI and FcγRIIA in the regulation of αIIbβ3‐mediated platelet activation to fibrinogen, thrombus buildup, and stability

  2021cites this paper
• Microfluidic chip grafted with integrin tension sensors for evaluating the effects of flowing shear stress and ROCK inhibitor on platelets

  2021cites this paper
• Mechanisms of thrombosis and research progress on targeted antithrombotic drugs.

  2021cites this paper
• Mind the gap: connexins and pannexins in platelet function

  2021cites this paper
• Vasoconstrictor and coagulation activator entrapped chitosan based composite hydrogel for rapid bleeding control.

  2021cites this paper
• Platelet plug formation in whole blood is enhanced in the presence of Porphyromonas gingivalis.

  2020cites this paper
• Integration of Rap1 and Calcium Signaling

  2020cites this paper
• Fibrin exposure triggers αIIbβ3‐independent platelet aggregate formation, ADAM10 activity and glycoprotein VI shedding in a charge‐dependent manner

  2020cites this paper
• Calcium in Cell-Extracellular Matrix Interactions.

  2020cites this paper
• Calcium chelation: a novel approach to reduce cryopreservation‐induced damage to frozen platelets

  2020cites this paper
• The molecular basis of platelet biogenesis, activation, aggregation and implications in neurological disorders

  2020cites this paper
• Synthesis And Pharmacological Evaluation Of Acylhydroquinone Derivatives As Potent Antiplatelet Agents.

  2020cites this paper
• A new method for accurate platelet thrombi volume measurement using a confocal microscope

  2019cites this paper
• Mechanisms of the antiplatelet and analgesic effects of dextromethorphan and its metabolites

  2019cites this paper
• Using extracellular calcium concentration and electric pulse conditions to tune platelet-rich plasma growth factor release and clotting.

  2019cites this paper
• Morin hydrate inhibits platelet activation and clot retraction by regulating integrin αIIbβ3, TXA2, and cAMP levels.

  2019cites this paper
• Biomechanical thrombosis: the dark side of force and dawn of mechano-medicine

  2019cites this paper
• Integrin αIIbβ3

  2019cites this paper
• Anti‑platelet activity of mineral‑balanced deep sea water is mediated via the regulation of Akt and ERK pathway crosstalk.

  2019cites this paper
• Can Yellow Stripe Scad Compete with Salmon on Its Role in Platelet Phospholipid Membrane and Its Cardiovascular Benefits?

  2019cites this paper
• An Active Micropump-mixer for Rapid Anti-platelet Drug Screening in Whole Blood.

  2019cites this paper
• Mechanism underlying N-(3-oxo-dodecanoyl)-L-homoserine lactone mediated intracellular calcium mobilization in human platelets.

  2019cites this paper
• Platelet preparation for function testing in the laboratory and clinic: Historical and practical aspects

  2019cites this paper
• ROLE OF CIB 1 IN PLATELET SIGNALING AND HEMOSTASIS

  2018cites this paper
• Effects of Surface Nanotopography and Calcium Chemistry of Titanium Bone Implants on Early Blood Platelet and Macrophage Cell Function

  2018cites this paper
• Integrating platelet and coagulation activation in fibrin clot formation

  2018cites this paper
• The Role of Serum Calcium Level in Intracerebral Hemorrhage Hematoma Expansion: Is There Any?

  2018cites this paper
• Connexins and Pannexins in Vascular Function and Disease

  2018cites this paper
• 14-3-3 proteins in platelet biology and glycoprotein Ib-IX signaling.

  2018cites this paper
• Effects of upstream shear forces on priming of platelets for downstream adhesion and activation.

  2018cites this paper
• Effects of the periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia on platelets

  2018cites this paper
• Activation of Discoidin Domain Receptors by collagen VI and collagen I fibrils

  2017cites this paper
• Developing Hybrid Polymer Scaffolds Using Peptide Modified Biopolymers for Cell Implantation.

  2017cites this paper
• Platelets and Immunity

  2017cites this paper
• Tumor necrosis factor-alpha induced caspase-3 activation-related iNOS gene expression in ADP-activated platelets

  2017cites this paper
• PLATELET ENDOCYTOSIS: ROLES IN HEMOSTASIS AND INNATE IMMUNITY

  2017cites this paper
• 119 – Platelet–Vessel Wall Interactions

  2017cites this paper
• Platelet populations and priming in hematological diseases.

  2017cites this paper
• Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis.

  2017cites this paper
• Secretome profiling of apheresis platelet supernatants during routine storage via antibody-based microarray.

  2017cites this paper
• Platelet Signalling: Calcium

  2017cites this paper
• (2017). Procoagulant platelets: - generation, function and therapeutic targeting in thrombosis. Blood , 130 (20), 2171-2179.

  2017cites this paper
• Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions

  2017cites this paper
• Improvement of quality standards for blood transfusions: use of functional measures to predict platelet transfusion efficacy

  2017cites this paper
• Zeroing in on red blood cell unit expiry

  2017cites this paper
• Platelet Morphology and Ultrastructure

  2017cites this paper
• Cryopreserved platelets demonstrate reduced activation responses and impaired signaling after agonist stimulation

  2017cites this paper
• Dual Biomembrane Force Probe enables single-cell mechanical analysis of signal crosstalk between multiple molecular species

  2017cites this paper
• Anxiety and Cardiovascular Disease: Epidemiology and Proposed Mechanisms

  2016cites this paper
• Cytokine-release kinetics of platelet-rich plasma according to various activation protocols

  2016cites this paper
• The Regulatory Activities of recombinant Properdin and TSP1 on Platelet and Complement activation

  2016cites this paper
• Electrical stimulation drives chondrogenesis of mesenchymal stem cells in the absence of exogenous growth factors

  2016cites this paper
• Platelet concentrate functionality assessed by thromboelastography or rotational thromboelastometry

  2016cites this paper
• Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation

  2016cites this paper
• Platelets — Allies of Tumour Cells

  2015cites this paper
• A Critical Role for the Transient Receptor Potential Channel Type 6 in Human Platelet Activation

  2015cites this paper
• IPA3 non-specifically enhances phosphorylation of several proteins in human platelets

  2015cites this paper
• Shear-induced platelet receptor shedding by non-physiological high shear stress with short exposure time: glycoprotein Ibα and glycoprotein VI.

  2015cites this paper
• Design of a pulsatile flow facility to evaluate thrombogenic potential of implantable cardiac devices.

  2015cites this paper
• Pathophysiology of Atherothrombosis — Thrombus Growth, Vascular Thrombogenicity, and Plaque Metabolism

  2015cites this paper
• Aspirin in diabetes mellitus: mechanisms and clinical implications

  2015cites this paper
• Shaping the platelet response to vascular injury

  2014cites this paper
• Zinc: An important cofactor in haemostasis and thrombosis

  2013cites this paper
• The Regulation of Platelet Life Span

  2013cites this paper
• Harnessing the platelet signaling network to produce an optimal hemostatic response.

  2013cites this paper
• Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner

  2013cites this paper
• signaling and GPIb-dependent thrombus formation in vivo Bruton tyrosine kinase is essential for botrocetin/VWF-induced

  2013cites this paper
• 3- and aggregation-independent manner β IIb α an Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in

  2013cites this paper
• Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry

  2013cites this paper
• Chapter 20 – Platelet Thrombus Formation in Flowing Blood

  2013cites this paper
• A multimode-TIRFM and microfluidic technique to examine platelet adhesion dynamics.

  2013cites this paper
• Pericellular Ca2+ recycling potentiates thrombin-evoked Ca2+ signals in human platelets

  2013cites this paper
• Diagnostic Assessment of Platelet Function

  2013cites this paper
• Differentiating haemostasis from thrombosis for therapeutic benefit

  2013influential citation