Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy
Abstract
:1. Introduction
2. GPIb-vWF-Axis
Reelin and PLD1 Are New Regulators of GPIb Signaling
3. ITAM-Signaling Pathways
3.1. GPVI Signaling
Reelin Amplifies GPVI Signaling in Platelets
3.2. CLEC-2 Signaling
4. G-Protein Coupled Receptor Activation—CXCRs as Emerging Modulators
CXCR Chemokine Receptors on Platelets Fine-Tune Thrombosis
5. Integrin Signaling in Platelets
5.1. Integrin Structure
5.2. Bidirectional Signaling of Integrin αIIbβ3: Role of Paxillin, Reelin and PLD1
6. Polymorphonuclear Leukocyte Released Platelet Agonists
7. Ion Channels: N-methyl-d-aspartate Glutamate Receptor (NMDAR) and Pannexin-1 (PANX1) as Modulators of Platelet Function
7.1. N-methyl-d-aspartate Glutamate Receptor (NMDAR)
7.2. Pannexin-1 (PANX1)
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AA | arachidonic acid |
ACS | acute coronary syndrome |
ADP | adenosine diphosphate |
ATP | adenosine triphosphate |
ApoER2 | apolipoprotein E receptor 2 |
APP | amyloid precursor protein |
Aβ | amyloid beta |
CAD | coronary artery diseases |
CCR1 (3, 4) | C-C chemokine receptor type 1 (3, 4) |
CLEC | C-type lectin-like receptor |
CNS | central nervous system |
CVD | cardiovascular diseases |
CXCL11 (12, 16) | C-X-C motif chemokine ligand 11 (12, 16) |
DEP | diesel exhaust particles |
DP1 | prostaglandin D2 receptor 1 |
DVT | deep vein thrombosis |
DTS | dense tubular system |
EC | endothelial cells |
EP1-4 | prostaglandin E2 receptors 1-4 |
Erk | extracellular stimuli-responsive kinase |
GPCR | G-protein-coupled-receptors |
GPIb | glycoprotein Ib |
GPO | glycine-proline-hydroxyproline |
GPVI | glycoprotein VI |
IL-6 | interleukin-6 |
ITAM | immunoreceptor tyrosine-based activation motif |
LAD | left anterior descending artery |
LAT | linker for the activation of T cells |
MI | myocardial infarction |
MIF | macrophage migration inhibitory factor |
MK | megakaryocytes |
NMDAR | N-methyl-D-aspartate receptor |
oxLDL | oxidized low density lipoprotein |
PA | phosphatidic acid |
PANX1 | pannexin-1 |
PDI | protein disulfide isomerase |
PGD2 | prostaglandin D2 |
PGE2 | prostaglandin E2 |
PGI2 | prostaglandin I2 |
PKC | protein kinase C |
PLATO | Platelet Inhibition and Patient Outcome |
PLCγ2 | phospholipase Cγ2 |
PLD | phospholipase D |
Prb | probenecid |
PS | phosphatidylserine |
SAP | stable angina pectoris |
SDF-1 | stromal cell-derived factor 1, CXCL12 |
SFK | Src family kinases |
SR | scavenger receptor |
TP | TXA2 receptor |
TxA2 | Thromboxane A2 |
VLDLR | very low density lipoprotein receptor |
vWF | von Willebrand factor |
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Classification | Integrin | GP Nomenclature | Ligands |
---|---|---|---|
β1-class | α2β1 | GPIa/IIa | collagen |
α5β1 | GPIc/IIa | fibronectin | |
α6β1 | GPIc‘/IIa | laminin | |
β3-class | αIIbβ3 | GPIIb/IIIa | fibrinogen, fibronectin, thrombospondin, vitronectin, von Willebrand factor |
αvβ3 | GPαv/IIIa | vitronectin, fibrinogen, fibronectin, collagen, osteopontin, thrombospondin, von Willebrand factor |
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Chatterjee, M.; Ehrenberg, A.; Toska, L.M.; Metz, L.M.; Klier, M.; Krueger, I.; Reusswig, F.; Elvers, M. Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy. Int. J. Mol. Sci. 2020, 21, 7906. https://doi.org/10.3390/ijms21217906
Chatterjee M, Ehrenberg A, Toska LM, Metz LM, Klier M, Krueger I, Reusswig F, Elvers M. Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy. International Journal of Molecular Sciences. 2020; 21(21):7906. https://doi.org/10.3390/ijms21217906
Chicago/Turabian StyleChatterjee, Madhumita, Agnes Ehrenberg, Laura Mara Toska, Lisa Maria Metz, Meike Klier, Irena Krueger, Friedrich Reusswig, and Margitta Elvers. 2020. "Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy" International Journal of Molecular Sciences 21, no. 21: 7906. https://doi.org/10.3390/ijms21217906