阿托伐他汀、阿司匹林对高血压患者血小板微粒CD62p、CD40L的影响

目的:探讨血小板膜糖蛋白微粒CD62p、CD40L与高血压的关系,以及他汀类、抗血小板药物对其影响。方法:采用流式细胞术(FCM)及单克隆抗体标记法,检测70例高血压患者(高血压组)、20例健康者(对照组)的血液标本,以20μmol/LADP为激活剂激活血小板,35例服用阿司匹林100mgQD,35例同时服用阿司匹林100mgQD和阿托伐他汀20mgQN,检测高血压患者血小板膜糖蛋白微粒CD62p、CD40L水平及药物对其作用。结果:高血压组CD62p、CD40L的百分率(85.3%±11.8%、69.2%±8.6%)比对照组(52.8%±7.6%、35.2%±5.4%)高(P<0.01),服用阿司匹林组CD62p、CD40L的百分率降至(64.2%±9.3%、47.7%±7.4%)与服药前有显著性差异(P<0.05),同时服用阿司匹林和阿托伐他汀组CD62p、CD40L的百分率降至(49.7%±9.8%、36.2%±5.1%)与服药前及只服用阿司匹林相比均差异有统计学意义(P<0.01)。结论:高血压与血小板膜糖蛋白微粒CD62p、CD40L的表达存在一定的联系,阿司匹林、阿托伐他汀可降低血小板微粒CD62...     

复方七芍降压片对SHR血压及GPⅡb/Ⅲa的影响

目的初步探讨复方七芍降压片的降压效果及血小板激活在动脉血栓形成机制中的中心作用。方法以12只14周龄WKY大鼠为阴性对照,60只14周龄自发性高血压大鼠(SHR)随机分为5组,分别采用尾动脉法测血压,采用酶联免疫吸附法测量血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)的含量。结果给药4周后,复方七芍降压片低、中、高剂量组及卡托普利组血压、GPⅡb/Ⅲa均有不同程度降低(P0.05),其中复方七芍降压片高剂量组疗效显著。结论复方七芍降压片能有效地降低SHR血压及GPⅡb/Ⅲa水平,其作用机制与复方七芍降压片调动血小板激活在动脉血栓形成机制中的中心作用有关。     

血小板GPⅡb／Ⅲa及其拮抗剂在冠心病临床实践的应用

本文介绍了血小板表面糖蛋白Ⅱｂ／Ⅲａ的结构功能及其拮抗剂在冠状动脉粥样硬化病临床实践的应用。     

血小板膜糖蛋白Ⅱb/Ⅲa基因多态性与脑梗死

脑血栓形成是在颈部大血管和脑内动脉存在粥样硬化斑块的基础上发生的,当斑块破裂时,损伤的血管内膜激活血小板,血小板、血管内皮下组织和血液中多种成分结合形成血栓,由此可见血小板在血栓形成中起了重要作用。各种诱导剂引起血小板聚集的通路不同。但是,所有导致血小板聚集的因素均依赖血小板膜糖蛋白(GP)Ⅱb/Ⅲa(GPⅡb/Ⅲa)的活化,活化的GPⅡb/Ⅲa与纤维蛋白原的结合是血小板聚集的最后通路。血小板膜GPⅡb/Ⅲa基因发生变异时,有可能改变血小板膜GPⅡb/Ⅲa结构和表达水平,进而影响血小板的黏附、聚集,影响血栓形成。本文将对GPⅡb/…     

血小板膜糖蛋白Ⅱb/Ⅲa受体靶向超声造影剂的制备及体外实验研究

目的:制备血小板膜糖蛋白(GP)Ⅱb/Ⅲa受体靶向超声造影剂,探讨其体外寻靶的作用。方法:将6-氨基肽与脂质体采用交连法合成GPⅡb/Ⅲa受体靶向微泡,观察其对血小板聚集形成的微血栓的黏附效应。体外实验分2组,将靶向微泡滴加于健康人新鲜血凝块上,光镜下观察微泡与血凝块的黏附情况。对照组采用普通造影剂。结果:体外实验:靶向微泡在血凝块外围形成凝聚带,并能延伸到血凝块内部,对照组均未见微泡与血凝块的结合。结论:血小板膜糖蛋白Ⅱb/Ⅲa受体特异性靶向微泡在体外对人新鲜血栓有趋附作用,且能特异结合。     

GPⅡb、GPⅢa在系膜增殖性肾小球肾炎中的表达

系膜增殖性肾炎 (ＭｓＰＧＮ)普遍存在肾小球毛细血管内凝血、白细胞浸润、系膜细胞增生和细胞外基质 (ＥＣＭ)进行性累积。ＥＣＭ累积又是导致肾小球硬化、肾衰竭的重要病理基础。整合素是介导组织修复、纤维化过程最密切的细胞黏附分子 ,其可以通过整合素影响肾小球硬化过程中的细胞增生。本研究在于了解 β3 整合素血小板膜糖蛋白Ⅱｂ、Ⅲａ(ＧＰⅡｂ、ＧＰⅢａ)在ＭｓＰＧＮ肾脏表达与ＥＣＭ的关系。共观察了18例肾功能正常的ＭｓＰＧＮ的电镜、光镜和免疫荧光下肾小球结构的变化 ,以及ＧＰⅡｂ、ＧＰⅢａ、Ｐ 选择素 (Ｐ 140 )和纤维连…     

血小板膜糖蛋白Ⅱb/Ⅲ a评估房颤并发血栓栓塞的临床价值

房颤患者血浆中血小板膜糖蛋白Ⅱb/Ⅲa含量明显增加,提示血小板激活是其发生血栓栓塞的因素之一.检测血小板膜糖蛋白Ⅱb/Ⅲa对于评估房颤患者血栓栓塞危险性,指导抗凝及减少栓塞事件的发生有重要的临床意义.     

血小板糖蛋白（GP）Ⅱb／Ⅲa受体拮抗剂在急性冠脉综合征中的应用

急性冠状动脉综合征（acute coronary syndrome,ACS）是由于不稳定斑块的破裂,引起冠状动脉内血栓形成所致急性心肌缺血的一组严重的进展性疾病谱,包括ST段抬高性心肌梗死（ST-elevation myocardial infarction,STEMI）、非ST段抬高性心肌梗死（non-ST-elevation myocardial infarction,NSTEMI）和不稳定型心绞痛（unstable angina,UA）,是冠状动脉疾病发病和死亡的主要原因。ACS的主要共同的病理生理学基础,为冠状动脉粥样斑块破裂的基础上形成血栓,不论血栓形成的启动因素为何,血小板的活化、粘附和聚集是动脉血栓形成过程中的关键步骤。因此,对ACS患者抗血小板治疗至关重要。     

GPⅡb／Ⅲa受体拮抗剂在急性冠脉综合征中的应用及对sCD40L的影响

不稳定斑块破裂和血小板聚集是急性冠脉综合征发生的基本机制。膜糖蛋白GPⅡb/Ⅲa受体拮抗剂可阻断血小板聚集的最后通路,并影响血清sCD40L的水平。现对此作一综述。     

血小板膜糖蛋白Ⅱb／Ⅲa拮抗剂─新型的抗血小板药

血小板膜糖蛋白Ⅱｂ／Ⅲａ拮抗剂有特异、高效抗血小板聚集作用，在治疗冠心病方面很有潜力。有一些类别在临床试验评价阶段取得了积极结果，其中Ｃ７Ｅ３已被联邦食品药品管理署批准用于临床。     

Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes.

This study examined the influence of the Pl(A) polymorphism of glycoprotein IIIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist, orbofiban, in patients with unstable coronary syndromes. Genotyping for the Pl(A) polymorphism was performed in 1014 patients recruited into the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction 16) trial, in which patients were randomized to low- or high-dose orbofiban or placebo for 1 year. The primary end point (n = 165) was a composite of death, myocardial infarction (MI), recurrent ischemia requiring rehospitalization, urgent revascularization, and stroke. Overall, orbofiban failed to reduce ischemic events when compared with placebo, but increased the rate of bleeding. In the whole population, Pl(A2) carriers had a significant increase in MI (n = 33) during follow up, with a relative risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P =.004). There was a significant interaction between treatment (placebo and orbofiban) and the Pl(A) polymorphism for bleeding (n = 187; P =.05). Thus, while orbofiban increased bleeding in noncarriers (RR = 1.87, 1.29 to 2.71; P <.001) in a dose-dependent fashion, it did not increase bleeding events in Pl(A2) carriers (RR = 0.87, 0.46 to 1.64). There was no interaction between treatment (placebo and orbofiban) and the Pl(A) polymorphism for the primary end point (P =.10). However, in the patients receiving orbifiban there was a higher risk of a primary event (RR = 1.55, 1.03 to 2.34; P =.04) and MI (RR 4.27, 1.82 to 10.03; P <.001) in Pl(A2) carriers compared with noncarriers. In contrast, there was no evidence that Pl(A2) influenced the rate of recurrent events in placebo-treated patients. In patients presenting with an acute coronary syndrome, the Pl(A) polymorphism of GPIIb/IIIa may explain some of the variance in the response to an oral GPIIb/IIIa antagonist.     

Platelets express a membrane protein complex immunologically related to the fibroblast fibronectin receptor and distinct from GPIIb/IIIa

We have previously identified and characterized a membrane glycoprotein complex (GP150/135) that functions as fibronectin receptor (FN-R) in fibroblast adhesion. Here we report that an immunologically related protein complex is expressed at the surface of human platelets. Antibodies monospecific for the smaller subunit (GP135) of the fibroblast FN-R in fact specifically stained the platelet surface, as determined by FACS analysis, and reacted with a component of molecular weight (mol wt) 138,000 as shown in western blots of platelet membranes. Moreover, the same antibodies precipitated the 138,000 component together with a 160,000 protein, suggesting that the two molecules are associated in a supramolecular complex. A comparative analysis indicated that this protein complex is distinct from the GPIIb/IIIa complex, known to function as a receptor of wide specificity for fibrinogen, fibronectin, and von Willebrand factor. Differential extraction experiments revealed that the platelet 138,000 component is an integral membrane protein.     

Progress in the field of GPIIb/IIIa antagonists

Platelet aggregation plays an important role in pathological situations such as myocardial infarction, unstable angina, peripheral artery disease, and stroke. Thus, pharmacological agents that specifically inhibit platelet aggregation are of great interest in the treatment and prevention of these cardiovascular diseases. Since binding of activated glycoprotein IIb/IIIa complex, a platelet surface integrin, to fibrinogen is the final step leading to platelet aggregation regardless of the initial stimulus, many researches have focused on the development of drugs that could antagonize this integrin. Three intravenous glycoprotein IIb/IIIa antagonists are currently marketed for the prevention of myocardial infarction in patients undergoing percutaneous intervention: Abciximab, Eptifibatide and Tirofiban. To further test the clinical efficacy of these agents, oral glycoprotein IIb/IIIa antagonists have been developed but only led to disappointing clinical results. Nevertheless, due to recognized usefulness of oral agents for the prevention and treatment of cardiovascular diseases, a great number of new orally active compounds are under clinical or preclinical evaluation. The aim of this review is to describe the chemical, pharmacological and clinical properties of existing and forthcoming glycoprotein IIb/IIIa antagonists.     

Comparison of the effects of cellulose triacetate and polysulfone membrane on GPIIb/IIIa and platelet activation

BACKGROUND: During hemodialysis session, several adverse reactions can occur on platelets, which are attributable to bioincompatibility of the dialysis membrane. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the receptor for fibrinogen, which mediates platelet aggregation and adhesion. Accordingly, we compared the influence of a cellulose triacetate (CTA) and polysulfone (PS) membrane on GPIIb/IIIa and platelet activation. METHODS: Blood samples from 5 patients on hemodialysis were taken at 0 time, 15 min, 30 min, 60 min and 240 min, during a single hemodialysis session, by a crossover design using CTA or PS. Platelet count and plasma concentration of GPIIb/IIIa, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were measured. GPIIb/IIIa was measured by flow cytometry. beta-TG and PF-4 were measured by ELISA. RESULTS: There was no significant change in the total amount of GPIIb/IIIa during dialysis session between the CTA and PS. However, the level of bound GPIIb/IIIa was significantly (p < 0.0002) increased from 1,426 +/- 435 to 40,446 +/- 2,777 mol/PLT with PS. In contrast, there was no significant change with CTA (3,258 +/- 1,469 to 4,301 +/- 1,422 mol/PLT). The platelet counts and beta-TG and PF-4 behavior during the dialysis session did not show significant change between the PS and CTA. CONCLUSION: The characterization of changes in platelet membrane receptor (GPIIb/IIIa) may be a useful marker for studying the biocompatibility of dialysis membranes. On platelet aggregation, CTA might be more biocompatible membrane than PS.     

Bridge to operation with the GPIIb/IIIa inhibitor abciximab in high-risk coronary patients

BACKGROUND: Glycoprotein-IIb/IIIa inhibitors are now frequently used in the cardiological treatment of high-risk coronary patients even if the patient is considered suitable for surgical intervention. However, there is no consensus whether GPIIb/IIIa inhibitors should be stopped before operation because of an increased risk of bleeding or if surgery should even be delayed until the anticoagulating effect subsides. METHODS: From June 2002 to August 2003 140 patients who had to undergo primary aorto-coronary bypass for ongoing myocardial ischemia were enrolled in the present study. The patients received either clopidogrel, aspirin and heparin or additionally abciximab until operation. RESULTS: Although the intraoperative need for blood products was higher in the abciximab group, there was no significant difference in postoperative blood loss. The hemodynamic situation of the abciximab patients after the operation was better compared to the other groups. 30-day mortality was not increased when compared to the elective control group (6.7 % vs. 6.1 %). CONCLUSION: The GPIIb/IIIa inhibitor abciximab can be safely used as a bridge to operation and results in a better hemodynamic outcome in high-risk coronary patients while reducing the incidence of major ischemic events.     

Localization of GPIb/IX and GPIIb/IIIa on Discoid Platelets

The organization and reorganization of mobile receptors, GPIIb/IIIa and GPIb/IX, on surface- and suspension-activated platelets have been studied in detail, but their distribution on resting, discoid platelets is uncertain. The present study has treated platelets in suspension with cytochalasin E before mounting on formvar grids or glass slide fragments in order to preserve their discoid appearance, then probed the organization of GPIIb/IIIa with fibrinogen coupled to gold particles (Fgn/Au) and GPIb/IX with bovine or ristocetin-activated human plasma detected by combined anti-vWF antibody and protein A coupled to gold particles. Multimers of vWF had the same tortuous, linear distribution from edge to edge observed previously on surface-activated platelets. However, the gold particles marking the complex of vWF-anti-vWF bound to GPIb/M were closer together on the discoid cells. Fgn/Au particles bound to GPIIb/IIIa receptors were uniformly distributed from edge to edge on many discoid platelets. On others they tended to clump or cluster in strips or patches. The latter organization of Fgn/Au-GPIIb/IIIa receptors may be due to the rugose nature of the discoid platelet surface or an influence of cytochalasin E. Definition of mobile receptor organization on discoid cells provides a useful baseline for determining their fate following surface or suspension activation.     

P-selectin,tissue factor and CD40 ligand expression on platelet-leucocyte conjugates in the presence of a GPIIb/IIIa antagonist

This study was to investigate the appearance of P-selectin, tissue factor (TF) and CD40 ligand (CD40L) on platelet-leucocyte conjugates in the absence and presence of a GPIIb/IIIa antagonist, MK-852, and the effect of adding EDTA to pre-formed conjugates. The purpose was to find out whether these antigens are displaced from the conjugates along with the platelets, thus providing information on their location. Hirudinized blood was stirred with collagen ((2?μg/mL) in the absence and presence of MK-852 (10?μmol/mL). P-selectin, TF and CD40L were measured on platelet-leucocyte conjugates (CD42a positive monocytes and neutrophils) and on single platelets by flow cytometry. Measurements were also made after subsequent addition of EDTA (4?mmol/L). Platelet-leucocyte conjugate formation was markedly enhanced in the presence of MK-852. P-selectin, TF and CD40L expression on the conjugates was also enhanced. Monocytes bound more platelets and expressed more P-selectin, TF and CD40L than neutrophils. EDTA displaced the majority of platelets from the conjugates and also the P-selectin, TF and CD40L, whereas it did not displaced P-selectin or CD40 ligand from platelets themselves. It is concluded that a GPIIb/IIIa antagonist promotes formation of platelet-leucocyte conjugates, which display P-selectin, TF and CD40L that appears to be associated with the adherent platelets. Platelet-monocyte conjugates are prime candidates for arterial inflammation and thrombosis. Pro-inflammatory and pro-thrombotic effects of CD40L and tissue factor may be an explanation of the negative clinical effects using GPIIb/IIIa antagonists.     

P-selectin, tissue factor and CD40 ligand expression on platelet-leucocyte conjugates in the presence of a GPIIb/IIIa antagonist

This study was to investigate the appearance of P-selectin, tissue factor (TF) and CD40 ligand (CD40L) on platelet-leucocyte conjugates in the absence and presence of a GPIIb/IIIa antagonist, MK-852, and the effect of adding EDTA to pre-formed conjugates. The purpose was to find out whether these antigens are displaced from the conjugates along with the platelets, thus providing information on their location. Hirudinized blood was stirred with collagen ((2 microg/mL) in the absence and presence of MK-852 (10 micromol/mL)). P-selectin, TF and CD40L were measured on platelet-leucocyte conjugates (CD42a positive monocytes and neutrophils) and on single platelets by flow cytometry. Measurements were also made after subsequent addition of EDTA (4 mmol/L). Platelet-leucocyte conjugate formation was markedly enhanced in the presence of MK-852. P-selectin, TF and CD40L expression on the conjugates was also enhanced. Monocytes bound more platelets and expressed more P-selectin, TF and CD40L than neutrophils. EDTA displaced the majority of platelets from the conjugates and also the P-selectin, TF and CD40L, whereas it did not displaced P-selectin or CD40 ligand from the platelets themselves. It is concluded that a GPIIb/IIIa antagonist promotes formation of platelet-leucocyte conjugates, which display P-selectin, TF and CD40L that appears to be associated with the adherent platelets. Platelet-monocyte conjugates are prime candidates for arterial inflammation and thrombosis. Pro-inflammatory and pro-thrombotic effects of CD40L and tissue factor may be an explanation of the negative clinical effects using GPIIb/IIIa antagonists.