P选择素在急性冠状动脉综合征中的研究进展

急性冠状动脉综合征主要包括不稳定型心绞痛、急性非Q波心肌梗死和Q波心肌梗死 ,占冠心病患者的 30 %～ 40 %。动脉粥样斑块的不稳定是急性冠状动脉综合征的主要原因。引起斑块不稳定的原因很多 ,其中包括斑块自身结构、斑块内出血、内皮功能损伤、炎症及免疫因素等。目前认为炎症过程在急性冠状动脉综合征的发病机制上起了关键性作用 ,参与了从白细胞的黏附到不稳定斑块的破裂及血栓的形成全过程。主要炎症标志物包括P选择素、白细胞介素 6(IL 6)、α 肿瘤坏死因子 (TNF α)、ICAM ,而P选择素介导活化血小板、内皮细胞与白细胞等的黏…     

P-选择素与静脉血栓栓塞症

血小板激活是静脉血栓形成的重要组成步骤,P-选择素是血小板的活性受体,也能被上皮细胞所识别.作为血小板/内皮细胞活化标志和细胞黏附受体.其可通过介导血小板、内皮细胞黏附及与白细胞的相互作用,启动参与包括炎症和血栓形成等多种病理生理起始过程,是血栓形成的重要介质和靶分子.检验P.选择素可以通过流式细胞仪检测血小板表面的P一选择素或通过酶联免疫吸附试验检测血液中可溶性P-选择素,方法简便,这些数据可作为血小板激活的判断.从而为血栓形成提供依据.抑制P一选择素及其配体的结合,可使病理状态下血栓局部白细胞聚集减少,细胞因子及组织因子表达降低,纤维蛋白生成减少,从而有助于抑制血栓的形成.     

P-选择素在心血管疾病中的临床意义

心血管疾病大多数是多因素疾病,其发生、发展或多或少与血小板的活化、白细胞的激活及内皮细胞的损伤有关,而P－选择素在其中发挥了重要作用。多个因素（如炎性因子、细胞因子、氧自由基等）从不同水平影响P－选择素的表达。近年研究表明P－选择素与动脉粥样硬化、心绞痛、心肌梗死、心肌缺血再灌注损伤及风湿性心脏病等心血管疾病密切相关。     

P-选择素、hsCRP在急性冠脉综合征中作用的研究新进展

急性冠脉综合征(ACS)是以冠状动脉粥样硬化斑块破裂或侵蚀所致的完全或不完全闭塞性血栓形成为病理基础的一组临床综合征。炎症介质P-选择素、高敏C反应蛋白(hsCRP)对ACS的病变程度、进展和预后有着非常重要的临床意义。本文对P-选择素、hsCRP与ACS发生发展有关的研究做一综述。     

血浆P选择素水平的性别差异

P选择素又称为血小板颗粒膜蛋白140(granule membrane protein-140,GMP-140),存在于血小板α颗粒,常作为血小板激活的检测指标[1].文献[2]报道,GMP-140也存在于内皮细胞Weibel-Palade体,已发现颈动脉粥样硬化时血浆水平升高[3].而内皮损伤与血小板激活是动脉粥样硬化斑块形成的重要机制.本研究观察了男女两组共40例健康体检人群的血浆P选择素水平变化,旨在探讨血浆P选择素的性别差异.     

P选择素与心血管疾病

P选择素(PADGEM,GMP140,CD62P)是细胞黏附分子选择素家族的重要成员,其介导的细胞黏附在机体炎性反应和血栓形成的初期起着主导作用。近年的研究表明,P选择素与心血管疾病的发生发展密切相关。1P选择素的结构与生物学特性P选择素最早于1984年在活化的血小板上发现,后来发现其亦     

P-选择素表达与心血管事件的中医药研究进展

心血管疾病是多因素病,它的发生发展与血小板活化、白细胞激活及内皮细胞损伤有关,其中P-选择素的作用尤为重要.近年来的研究表明不少中药可影响P-选择素表达及心血管疾病的进展.     

黏附分子细胞间黏附分子-1/E-选择素与冠心病

冠心病是一种高发病率和高病死率的疾病,炎症反应在冠状动脉粥样硬化斑块的形成中起着重要作用。活化的血管内皮细胞分泌的细胞黏附分子,如细胞间黏附分子-1和E-选择素等,它们介导内皮细胞与白细胞、血小板间的起始黏附,促进血液循环中白细胞、血小板黏附于血管内皮,引起炎症反应、血栓形成等,在动脉粥样硬化和冠心病的发生、发展中起重要作用。     

P选择素与炎症性肠病

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),目前认为血小板功能异常在其发病机制及发展过程中起着重要作用.P选择素是细胞黏附分子中选择素家族成员,介导血小板活化及炎症反应等.研究表明P选择素在炎症性肠病的病理过程中起重要作用.     

P—选择素与糖尿病血管病变

糖尿病并发血管病变与血小板活化及内皮受损、血管内皮功能减退密切相关。近年研究证实，P—选择素通过促进白细胞与血小板和内皮细胞的粘附造成内皮损伤和血管内微血栓形成，在糖尿病大血管病变、糖尿病微血管病变的发生发展中具有重要作用。P—选择素及其单克隆抗体的研究将为临床诊治糖尿病血管病变提供新的思路。     

Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture

Objectives. The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation.Background. It is likely that the nature of the substrate exposed after spontaneous or angioplasty-induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established.Methods. We investigated thrombus formation on foam cell-rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen-poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [±SEM] activated partial thromboplastin time ratio 1.5 ± 0.04) for 5 min under high shear rate conditions (1,690 s⁻¹). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated.Results. Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagenrich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p = 0.002).Conclusions. The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content.     

Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi.

Ruptured atheromatous plaques were identified by step-sectioning technique as responsible for 40 of 51 recent coronary artery thrombi and 63 larger intimal haemorrhages. The degree of pre-existing luminal narrowing at the site of rupture was decisive for whether plaque rupture caused occlusive thrombosis or just intimal haemorrhage. If the pre-existing stenosis was greater than 90% (histologically determined) then plaque rupture nearly always caused occlusive thrombosis. Clearly indicating the primary role of plaque rupture in thrombus formation were the frequent finding of plaque fragments deeply buried in the centre of the thrombus and the nature of the thrombus at the site of rupture where it consisted predominantly of platelets. Thus, a severe chronic stenosis seems to be a prerequisite for occlusive thrombus formation, but the thrombotic process itself is triggered by an acute intimal lesion.     

Physiopathology of unstable angina

The major risk of atherosclerotic disease is the occurrence of an acute coronary syndrome. The pathogenesis of instable angina involves the formation of an arterial thrombus as a consequence of the rupture of an atheromatous plaque. This risk of plaque rupture appears to depend on plaque morphology rather than plaque size or severity of stenosis. Ratio of lipid core to fibrous determined by the balance between smooth muscle cells proliferation and extracellular matrix synthesis stabilizing the plaque and macrophages which degrade collagen, determine the plaque vulnerability. The fibrous cap weakness leads to the plaque activation, plaque fissure or erosion activating a thrombotic cascade. A general inflammation or prothrombotic states are probably involved suggesting the need for a systemic therapeutic in addition with the treatment of the culprit lesion.     

Atheromatous plaque in the distal aortic arch creating the potential for cerebral embolism during cardiopulmonary bypass

The present study evaluated the risk in cardiac patients of rupture of a plaque by a jet stream from the arch cannula. The entire thoracic aorta and cardiac function were routinely monitored by transesophageal echocardiography (TEE) in 88 adult patients who underwent coronary artery bypass surgery. The changes in the atheromatous plaque in the distal aortic arch were observed before and after cardiopulmonary bypass. Of the 88 patients, 13 were found to have preoperative atheromatous plaque at the distal aortic arch and 8 (61.5%) of them suffered plaque rupture caused by jet stream from the arch cannula. Only 1 patient experienced apparent embolic episodes manifesting as cerebral and left leg embolisms; the remaining 7 had no clinical embolic symptoms. In order to prevent atheroembolic events, attention should be paid not only to the ascending aorta, but also to the distal arch and in this regard TEE is useful for detecting atheromatous changes of the aorta.     

Relationship between myocardial infarction and preinfarction angina: a histopathological study of coronary arteries in two sudden death cases employing serial section

Two patients who had previously experienced old myocardial infarction and who died suddenly after an attack of chest pain were examined and discussed. In both cases two of the three main coronary arteries showed severe stenosis with canalization. Ruptured atheromatous plaque was found in the unblocked coronary artery. Fibrin was already formed and surrounded the fractured intimal collagen fiber, foam cells, and cholesterin clefts, but a luminal thrombi had not yet been formed. Fresh occluding thrombi were formed at the site of the ruptured atheromatous plaque. Coronary thrombi containing abscess components such as foam cells, cholesterin clefts, and the fractured intimal collagen fiber were found in our preliminary study. These views support the supposition that this fracture between the lumen and the plaque might precede and be responsible for the formation of the thrombus and the onset of acute myocardial infarction. It was confirmed that the attack of preinfarction angina occurred at the time of the rupture of the atheromatous plaque. The rupture of the atheromatous plaque plays an important part as an initiating factor of peinfarction angina and myocardial infarction. Thus, it is necessary to examine coronary arteries by serial histopathological section method.     

Coronary thrombosis in pathogenesis of acute myocardial infarction. Histopathological study of coronary arteries in 108 necropsied cases using serial section

An extensive histopathological study was carried out on the hearts of 108 patients with electrocardiographically proven acute myocardial infarction dying after admission to a coronary care unit. The occluded or the narrowest segments of the coronary arteries were examined at intervals of 100 mu using serial sections. Serial sectioning is important in such a study because the pathology of the lumen can vary considerably within a 2 to 3 mm segment. A high incidence (80.3%) of thrombus formation corresponding to the site of infarction was observed. These thrombi occluded the vessel lumen, were usually found proximally in the coronary arteries, and were associated with a ruptured atheromatous plaque in 90.8 per cent of cases. It is postulated that an increase of intraplaque pressure resulting from a honeycomb-like accumulation of foam cells, cholesterol clefts, and blood infiltration through the injured endothelial cells is the cause of rupture of the atheromatous plaque. This rupture into the vessel lumen may precede, and be responsible for, formation of thrombus and the onset of acute myocardial infarction.     

Coronary thrombosis in pathogenesis of acute myocardial infarction. Histopathological study of coronary arteries in 108 necropsied cases using serial section.

An extensive histopathological study was carried out on the hearts of 108 patients with electrocardiographically proven acute myocardial infarction dying after admission to a coronary care unit. The occluded or the narrowest segments of the coronary arteries were examined at intervals of 100 mu using serial sections. Serial sectioning is important in such a study because the pathology of the lumen can vary considerably within a 2 to 3 mm segment. A high incidence (80.3%) of thrombus formation corresponding to the site of infarction was observed. These thrombi occluded the vessel lumen, were usually found proximally in the coronary arteries, and were associated with a ruptured atheromatous plaque in 90.8 per cent of cases. It is postulated that an increase of intraplaque pressure resulting from a honeycomb-like accumulation of foam cells, cholesterol clefts, and blood infiltration through the injured endothelial cells is the cause of rupture of the atheromatous plaque. This rupture into the vessel lumen may precede, and be responsible for, formation of thrombus and the onset of acute myocardial infarction.     

The complement factor properdin induces formation of platelet-leukocyte aggregates via leukocyte activation

Both the complement system and platelet-leukocyte aggregates are involved in chronic and acute stages of atherosclerosis. Properdin, a positive regulator of the complement system, is secreted by leukocytes and endothelial cells. In the present study, the role of properdin in the formation of platelet-leukocyte aggregates was investigated. Incubation of human whole blood with properdin (25–200 µg/ml) resulted in a dose-dependent formation of platelet-leukocyte aggregates, with an increase of up to 2.2-fold compared to controls (p < 0.05), as analysed by flow cytometry. In addition, properdin significantly amplified ADP-induced aggregation of platelets with leukocytes by 53% (p < 0.05), while it had no effect on ADP-induced aggregation of platelets alone. Consistent with these results, properdin did not activate platelets as shown by the expression of activated GPIIb/IIIa (PAC-1 epitope) and P-selectin (CD62P) on the platelet surface. However, properdin significantly induced expression of CD11b (MAC-1) on leukocytes by 12-fold (p < 0.05) as a measure of leukocyte activation. In conclusion, the complement system component properdin induces the formation of platelet-leukocyte aggregates via leukocyte activation. The data establish a link between the complement system and platelet-leukocyte aggregates with potential significance in atherosclerotic vascular disease.     

Platelets and Atherothrombosis: An Essential Role for Inflammation in Vascular Disease — A Review

Atherothrombosis is the common link between clinical manifestations of arterial vascular disease including ischemic stroke and acute coronary syndromes, such as unstable angina and acute myocardial infarction. Our understanding of the common pathologic mechanisms underlying these conditions has significantly increased during the past ten years, yet atherothrombosis as the “root cause” of a large proportion of cardiovascular and cerebrovascular diseases is largely underappreciated. Although the classical risk factors of dyslipidemia, smoking, diabetes, hypertension, obesity, and sedentary lifestyle are widely recognized as being associated with a heightened risk of vascular disease, inflammation of the vascular system during the past decade has become increasingly regarded as the principal underlying mechanism in the development of clinical atherothrombotic disease. In addition, platelet-derived inflammatory mediators play an essential role in the pathogenesis of cardiovascular disease, being involved at all stages of plaque development until their eventual rupture and subsequent formation of a platelet-rich thrombus. Mounting evidence supports the role of both localized and systemic inflammation in these events. Platelets are central to vascular inflammatory processes. Thus, inflammation can stimulate local thrombosis and thrombosis can amplify inflammation. Consequently, antiplatelet therapy for the prevention of serious vascular events may provide a double benefit via an anti-inflammatory action of the antiplatelet agent in modifying plaque formation and stability and antiplatelet activity that inhibits platelet aggregation and thrombus formation from occurring following plaque rupture.     

Fibrin and atherogenesis--a hypothesis

It has recently been found that endothelial cells exhibit an unusual change in cellular behavior in response to contact with fibrin. The possible implications of this finding with regard to the mechanism of atherogenesis are discussed. It is proposed that mural fibrin in vivo may produce a disorganized endothelium which can act as a nidus for further fibrin deposition and platelet aggregation. In the presence of inadequate fibrinolysis, a prolonged endothelial lesion could occur which may eventually result in atheromatous plaque formation. This view of atherogenesis requires reduced fibrinolytic activity as a prerequisite for plaque formation, a requirement which is in agreement with currently known data associating atherogenic risk factors with inhibited fibrinolysis.