• 제목/요약/키워드: Glycoprotein-IIb/IIIa inhibitor

검색결과 5건 처리시간 0.017초

Effect of Cordycepin-Enriched WIB801C from Cordyceps militaris Suppressing Fibrinogen Binding to Glycoprotein IIb/IIIa

  • Lee, Dong-Ha;Kim, Hyun-Hong;Lim, Deok Hwi;Kim, Jong-Lae;Park, Hwa-Jin
    • Biomolecules & Therapeutics
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    • 제23권1호
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    • pp.60-70
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    • 2015
  • In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

Total saponin from Korean Red Ginseng inhibits binding of adhesive proteins to glycoprotein IIb/IIIa via phosphorylation of VASP (Ser157) and dephosphorylation of PI3K and Akt

  • Kwon, Hyuk-Woo;Shin, Jung-Hae;Cho, Hyun-Jeong;Rhee, Man Hee;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • 제40권1호
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    • pp.76-85
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    • 2016
  • Background: Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$. Methods: We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$, and clot retraction. Results: KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via phosphorylation of VASP ($Ser^{157}$), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS-increased VASP ($Ser^{157}$) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of ${\alpha}IIb/{\beta}3$ activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of $[Ca^{2+}]_i$ mobilization and increase of cAMP production. Conclusion: These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$, and clot retraction, and may prevent platelet ${\alpha}IIb/{\beta}3$-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS.

Current Opinion on Endovascular Therapy for Emergent Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis

  • Dong-Hun Kang;Woong Yoon
    • Korean Journal of Radiology
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    • 제20권5호
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    • pp.739-748
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    • 2019
  • For recanalization of emergent large vessel occlusions (ELVOs), endovascular therapy (EVT) using newer devices, such as a stent retriever and large-bore catheter, has shown better patient outcomes compared with intravenous recombinant tissue plasminogen activator only. Intracranial atherosclerotic stenosis (ICAS) is a major cause of acute ischemic stroke, the incidence of which is rising worldwide. Thus, it is not rare to encounter underlying ICAS during EVT procedures, particularly in Asian countries. ELVO due to underlying ICAS is often related to EVT procedure failure or complications, which can lead to poor functional recovery. However, information regarding EVT for this type of stroke is lacking because large clinical trials have been largely based on Western populations. In this review, we discuss the unique pathologic basis of ELVO with underlying ICAS, which may complicate EVT procedures. Moreover, we review EVT data for patients with ELVO due to underlying ICAS and suggest an optimal endovascular recanalization strategy based on the existing literature. Finally, we present future perspectives on this subject.

Intra-arterial and Intravenous Tirofiban Infusion for Thromboembolism during Endovascular Coil Embolization of Cerebral Aneurysm

  • Kim, Sang Heum;Kim, Tae Gon;Kong, Min Ho
    • Journal of Korean Neurosurgical Society
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    • 제60권5호
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    • pp.518-526
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    • 2017
  • Objective : Thromboembolism is the one of the most serious complications that can occur during endovascular coil embolization of cerebral aneurysm. We report on the effectiveness and safety of intra-arterial/intravenous (IA/IV) glycoprotein IIb/IIIa inhibitor (tirofiban) infusion for treating thromboembolism during endovascular coil embolization of cerebral aneurysm. Methods : We performed a retrospective analysis of 242 patients with ruptured or unruptured cerebral aneurysms (n=264) who underwent endovascular coil embolization from January 2011 to June 2014. Thromboembolism occurred in 20 patients (7.4%), including 14 cases of ruptured aneurysms and 6 cases of unruptured aneurysms. The most common site of aneurysms was the anterior communicating artery (n=8), followed by middle cerebral artery (n=6). When we found an enlarged thromboembolism during coil embolization, we tried to dissolve it using tirofiban administered via IA and IV loading ($5{\mu}g/kg$, respectively) for 3-5 minutes followed by IV maintenance ($0.08{\mu}g/kg/min$) for approximately 4-24 hours. Results : In 4 of 5 patients with total vessel occlusion, the vessel was recanalized to Thrombolysis in Cerebral Infarction Perfusion Scale (TICI) grade 3, and in 1 patient to TICI grade 2a. In 2 patients with partial vessel occlusion and 13 patients with minimal occlusion, the vessel recanalized to TICI grade 3. Irrelevant intracerebral hemorrhage was noted in 1 patient (5%), and thromboemboli-related cerebral infarction developed in 5 patients (25%), of which only 1 (5%) was symptomatic. Conclusion : IA/IV infusion and IV maintenance with tirofiban appear to be an effective rescue treatment for thromboembolism during endovascular coil embolization in patients with ruptured or unruptured cerebral aneurysms.