Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.7K
Formation of the Platelet Plug01:22

Formation of the Platelet Plug

5.8K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
5.8K
Activation of Integrins01:15

Activation of Integrins

3.4K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.4K
Extrinsic and Intrinsic Pathways of Hemostasis01:20

Extrinsic and Intrinsic Pathways of Hemostasis

7.1K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
7.1K
Integrins01:10

Integrins

3.9K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
3.9K
Clot Retraction and Fibrinolysis01:16

Clot Retraction and Fibrinolysis

5.4K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
5.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Current opinion: the OCEANIC trial journey: from failure to breakthrough?

European heart journal. Cardiovascular pharmacotherapy·2026
Same author

Antidotes for Anticoagulation Reversal.

The New England journal of medicine·2026
Same author

Advanced glycation end product (AGE)-modified albumin does not enhance neutrophil extracellular trap formation and minimally impacts endothelial inflammation in large vessels.

Life sciences·2026
Same author

Adaption of the plasmin generation assay to enhance sensitivity to plasminogen activator inhibitor-1 and establishment of sex-specific reference values in human plasma.

Research and practice in thrombosis and haemostasis·2026
Same author

Single-domain antibodies to reverse the effects of factor Xa inhibitors on coagulation tests.

Journal of thrombosis and haemostasis : JTH·2026
Same author

Thrombophilia Screening in Young Patients With Cryptogenic Ischemic Stroke.

Stroke·2026
Same journal

Venous Thromboembolism Prophylaxis and Postoperative Outcomes in Persons with Bleeding Disorders Undergoing Major Surgery: A Canadian Pilot Feasibility Study.

TH open : companion journal to thrombosis and haemostasis·2026
Same journal

Combined Effect of Hemoglobin Levels and Obesity on the Risk of Incident Venous Thromboembolism: The Tromsø Study.

TH open : companion journal to thrombosis and haemostasis·2026
Same journal

Edoxaban versus Apixaban Outcomes Differences in 8,444 Patients with Atrial Fibrillation from Italy: A Real-World Use Comparison.

TH open : companion journal to thrombosis and haemostasis·2026
Same journal

Cross-Reactivity of Antiphospholipid Antibodies with Gut Commensal Proteins in Antiphospholipid Syndrome.

TH open : companion journal to thrombosis and haemostasis·2026
Same journal

Individual Comparative PK Evaluation of Single-dose Octocog Alfa, Rurioctocog Alfa Pegol, and Efanesoctocog Alfa in Adults with Severe Hemophilia A.

TH open : companion journal to thrombosis and haemostasis·2026
Same journal

Differential Regulation of Granule Release in Platelets and Immune Cells.

TH open : companion journal to thrombosis and haemostasis·2026
See all related articles

Related Experiment Video

Updated: Jun 23, 2025

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers
05:43

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Published on: November 8, 2024

307

Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation.

Jinmi Zou1,2, Siyu Sun1,2, Ilaria De Simone1

  • 1Platelet (patho)physiology, Synapse Research Institute, Maastricht, The Netherlands.

TH Open : Companion Journal to Thrombosis and Haemostasis
|June 24, 2024
PubMed
Summary
This summary is machine-generated.

Protein kinase C (PKC) and autocrine adenosine diphosphate (ADP) signaling stabilize platelet aggregation by maintaining integrin αIIbβ3 activation. Inhibiting these pathways can reverse this activation, offering insights for antiplatelet therapies.

Keywords:
P-selectinglycoprotein VIintegrin αIIbβ3protease-activated receptorsprotein kinase C

More Related Videos

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

7.6K
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
04:15

Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation

Published on: February 2, 2024

1.8K

Related Experiment Videos

Last Updated: Jun 23, 2025

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers
05:43

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Published on: November 8, 2024

307
A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

7.6K
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
04:15

Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation

Published on: February 2, 2024

1.8K

Area of Science:

  • Hematology
  • Molecular Biology
  • Pharmacology

Background:

  • Agonist-induced platelet activation involves integrin αIIbβ3 conformational change, crucial for fibrinogen binding and aggregation.
  • The signaling pathways determining permanent versus transient platelet activation states remain incompletely understood.
  • Understanding these pathways is key to elucidating reversible platelet aggregation phases.

Purpose of the Study:

  • To investigate platelet signaling mechanisms regulated by glycoprotein VI (GPVI) and protease-activated receptors (PAR) for thrombin.
  • To explore how these receptors influence time-dependent integrin αIIbβ3 activation.
  • To identify signaling pathways controlling the reversibility of platelet activation.

Main Methods:

  • Platelets were activated using collagen-related peptide (CRP) for GPVI, and thrombin receptor-activating peptides or thrombin for PAR1/PAR4.
  • Integrin αIIbβ3 activation and P-selectin expression were measured via flow cytometry.
  • Signaling pathway inhibitors were applied pre- and post-agonist stimulation; platelet spreading was assessed using microscopy.

Main Results:

  • Inhibitor pretreatment revealed a hierarchy of protein kinase C (PKC) > glycogen synthase kinase 3 > β-arrestin > phosphatidylinositol-3-kinase in reducing GPVI/PAR-induced activation.
  • Posttreatment showed secondary αIIbβ3 inactivation (but not P-selectin expression) for CRP and PAR1 agonists, following the same inhibitor order.
  • Combined PKC inhibition, P2Y12 receptor blockade with ticagrelor, and PAR1/GPVI stimulation enhanced αIIbβ3 inactivation and altered platelet morphology.

Conclusions:

  • PKC and autocrine ADP signaling are critical for sustained integrin αIIbβ3 activation, particularly after PAR1/GPVI stimulation.
  • These pathways contribute to stabilized platelet aggregation, with implications for antiplatelet drug efficacy.
  • Targeting PKC and P2Y12 pathways offers potential for modulating platelet activation reversibility.