The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries
Open accessAbstract
The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40-50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic process. P2Y12-null mice were generated by a gene-targeting strategy. Using an in vivo mesenteric artery injury model and real-time continuous analysis of the thrombotic process, we observed that the time for appearance of first thrombus was delayed and that only small, unstable thrombi formed in P2Y12-/- mice without reaching occlusive size, in the absence of aspirin. Platelet adhesion to vWF was impaired in P2Y12-/- platelets. While adhesion to fibrinogen and collagen appeared normal, the platelets in thrombi from P2Y12-/- mice on collagen were less dense and less activated than their WT counterparts. P2Y12-/- platelet activation was also reduced in response to ADP or a PAR-4-activating peptide. Thus, P2Y12 is involved in several key steps of thrombosis: platelet adhesion/activation, thrombus growth, and stability. The data suggest that more aggressive strategies of P2Y12 antagonism will be antithrombotic without the requirement of aspirin cotherapy and may provide benefits even to the aspirin-nonresponder population.
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(1996) · The Lancet · doi:10.1016/s0140-6736(96)09457-3 · Cited by 6,503
(2001) · New England Journal of Medicine · doi:10.1056/nejmoa010746 · Cited by 6,470
Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
Angelillo-Scherrer, A., de Frutos, P. G., Aparicio, C., Melis, E., Savi, P., Lupu, F., Arnout, J., Dewerchin, M., Hoylaerts, M. F., Herbert, J.-M., et al. (2001) · Nature Medicine · doi:10.1038/84667 · Cited by 441 · cited 1×
“As platelets release thrombogenic mediators such as CD40L and Gas6 upon activation (28, 29), this could further reduce the thrombogenicity of a P2Y12 growing thrombus.”
Background
Cited by
Platelet Activation and Atherothrombosis
Davì, G., & Patrono, C. (2007) · New England Journal of Medicine · doi:10.1056/nejmra071014 · Cited by 2,135
The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W.-B., & Julius, D. (2006) · Nature Neuroscience · doi:10.1038/nn1805 · Cited by 1,542
Negative feedback control of neuronal activity by microglia
Badimon, A., Strasburger, H. J., Ayata, P., Chen, X., Nair, A., Ikegami, A., Hwang, P., Chan, A. T., Graves, S. M., Uweru, J. O., et al. (2020) · Nature · doi:10.1038/s41586-020-2777-8 · Cited by 979
Activation of Platelet Function Through G Protein–Coupled Receptors
Offermanns, S. (2006) · Circulation Research · doi:10.1161/01.res.0000251742.71301.16 · Cited by 725
Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier
Lou, N., Takano, T., Pei, Y., Xavier, A. L., Goldman, S. A., & Nedergaard, M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520398113 · Cited by 364
Metadata
- Authors
- André, P., Delaney, S. M., LaRocca, T., Vincent, D., DeGuzman, F., Jurek, M., Koller, B., Phillips, D. R., & Conley, P. B.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-08-01
- Volume
- 112
- Issue
- 3
- Pages
- 398-406
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2144095528
- Cited by
- 359
- References
- 3
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- bronze
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- André, P., Delaney, S. M., LaRocca, T., Vincent, D., DeGuzman, F., Jurek, M., Koller, B., Phillips, D. R., & Conley, P. B. (2003). P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. Journal of Clinical Investigation. https://doi.org/10.1172/jci17864
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