Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor γ-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury

Takaya, Norihide; Katoh, Youichi; Iwabuchi, Kazuhisa; Hayashi, Ichiro; Konishi, Hakuoh; Itoh, Seigo; Okumura, Ko; Ra, Chisei; Nagaoka, Isao; Daida, Hiroyuki

doi:10.1016/j.yjmcc.2005.07.006

Cited by 40 publications

(32 citation statements)

References 33 publications

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“…We have recently shown that fucoidan is a novel agonist for CLEC-2 (34), and our studies show that fucoidan can induce normal platelet aggregation and Syk phosphorylation in RhoG-deficient platelets. Because fucoidan activates ITAM and Syk phosphorylation signaling independently of the GPVI-FcR␥ complex, our findings demonstrate the involvement of RhoG in the signaling pathways mice have impaired occlusive platelet microthrombi and that Syk phosphorylation is inhibited, but no difference was found in bleeding time between WT and knock-out mice (36). However, the mechanism through which FcR␥ regulates RhoG recruitment and activation downstream of GPVI is unclear.…”

Section: Discussionmentioning

confidence: 72%

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

Kim

Dangelmaier

Bhavanasi

et al. 2013

Journal of Biological Chemistry

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Background: RhoG is a ubiquitously expressed member of the Rho family of GTPases. Results: RhoG-deficient platelets display severely impaired GPVI-dependent platelet activation. Conclusion: RhoG plays an important role in GPVI-FcR␥ complex-mediated platelet activation and thrombus formation. Significance: Our study enhances the understanding of the molecular mechanisms of GPVI-FcR␥ complex activation.

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Section: Discussionmentioning

confidence: 72%

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

Kim

Dangelmaier

Bhavanasi

et al. 2013

Journal of Biological Chemistry

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“…Similarly, blocking collagen with anti-collagen antibodies or degrading it with collagenase, prevents thrombus formation. Platelets activated by collagen via FcR also have a major role in myocardial ischemiareperfusion injury [86]. All these studies reinforce the idea that GPVI is a potential target for antithrombotic therapy.…”

Section: Gpvi: Animal Modelsmentioning

confidence: 70%

Collagen Receptors as Potential Targets for Novel Anti-Platelet Agents

Clemetson

Clemetson²

2007

CPD

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Platelets have important roles in atherosclerosis and thrombosis and their inhibition reduces the risk of these disorders. There is still a need for platelet inhibitors affecting pathways that reduce thrombosis and atherosclerosis while leaving normal hemostasis relatively unaffected, thus reducing possible bleeding complications. Although combinations show progress in achieving these goals none of the present inhibitors completely fulfill these requirements. Collagen receptors offer attractive possibilities as alternative targets at early stages in platelet activation. Three major collagen receptors are assessed in this review; the alpha2beta1 integrin, responsible primarily for platelet adhesion to collagen; GPVI, the major signaling receptor for collagen; and GPIb-V-IX, which is indirectly a collagen receptor via von Willebrand factor. Several thrombosis models and experimental approaches suggest that all three are interesting targets and merit further investigation.

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“…During these interventions the endothelium remains intact and thus ligands originating from the subendothelial layers are unlikely to be binding partners for platelet receptors mediating platelet adhesion (31). One study (55), however, reports disruption of endothelial cells. However, the authors do not provide direct evidence for exposure of collagen under I/R.…”

Section: Discussionmentioning

confidence: 99%

The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice

Schönberger

Ziegler

Borst

et al. 2012

American Journal of Physiology-Cell Physiology

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Platelets play a critical role in the pathophysiology of reperfusion, sepsis, and cardiovascular diseases. In a multiple step process, they adhere to activated endothelium and release proinflammatory cytokines thereby promoting the inflammatory process. Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and triggers platelet activation and primary hemostasis. Activation of GPVI leads to stable platelet adhesion and degranulation of platelet granules. However, GPVI is critically involved in platelet adhesion to activated endothelium without exposure of subendothelial matrix. Earlier studies show that the soluble GPVI-Fc binds to collagen and protects mice from atherosclerosis and decreases neointima proliferation after arterial injury. Here, we show for the first time that recombinant GPVI-Fc binds to activated endothelium mainly via vitronectin and prevents platelet/endothelial interaction. Administration of GPVI-Fc reduced infarct size and preserved cardiac function in a mouse model of myocardial infarction. This process was associated with reduced GPVI-induced platelet degranulation and release of proinflammatory cytokines in vitro and in vivo. Taken together, administration of GPVI-Fc offers a novel strategy to control platelet-mediated inflammation and to preserve myocardial function following myocardial infarction.

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Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor γ-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury

Cited by 40 publications

References 33 publications

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

Collagen Receptors as Potential Targets for Novel Anti-Platelet Agents

The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice

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