不稳定斑块发生机制及影响因素

不稳定斑块是急性冠脉综合征发生的主要原因,现就不稳定斑块的产生过程及其斑块破裂后血栓形成的主要影响因素进行综述.     

不稳定性动脉粥样硬化斑块的特点及主要形成机制

动脉粥样硬化斑块的不稳定是导致斑块破裂、溃疡致使动脉内血栓形成从而引起卒中的主要发病机制,具有极大的危害性。深入研究不稳定性斑块的形成机制、影响因素和临床标志物对于稳定斑块、治疗和预防心脑血管疾病有着极其重要的意义。     

不稳定性动脉粥样硬化斑块的特点及主要形成机制

动脉粥样硬化斑块的不稳定是导致斑块破裂、溃疡致使动脉内血栓形成从而引起卒中的主要发病机制，具有极大的危害性：深入研究不稳定性斑块的形哎机制、影响因素和临床标志物对于稳定斑块、治疗和预防心脑血管疾病有蕾极其重要的意义．     

急性冠脉综合征的抗炎治疗新进展

急性冠状动脉综合征（ACS）是冠心病的特殊疾病谱，是由不稳定的粥样硬化斑块破裂激发血栓形成所致的急性心肌缺血综合征，包括不稳定型心绞痛（UA）、非ST段抬高心肌梗死（NSTEMI）和ST段抬高心肌梗死（STEMI）。近年来的研究证实，ACS的发生与冠状动脉的狭窄程度无直接相关，而与斑块的不稳定及继发的血栓形成密切相关，而炎症是引起斑块不稳定和继发血栓形成决定性的因素之一。如何减少炎症在ACS发生时对易损斑块的不良影响，对ACS进行有效治疗，已成为临床医生和研究人员的重要研究目标。     

不稳定斑块的基因治疗

不稳定斑块易破裂，出血以及继发血栓形成，是引起急性冠脉综合征的主要原因，斑块不稳定主要与其病理特点有关，本文结合不稳定斑块形成的原因，综述近年来基因治疗在增强不稳定斑块稳定性，减少斑块破裂中的作用。     

急性冠脉综合征的炎症机制

炎症在动脉粥样硬化的发生发展及其并发症的发病机制中起重要作用[1～2],炎症是引起斑块不稳定的主要因素,参与了从白细胞的黏附到斑块的破裂及血栓形成的全过程.     

稳定冠状动脉粥样硬化斑块新策略

冠状动脉粥样硬化斑块的生物学特性是决定其稳定的主要因素,不稳定斑块块破裂及继发血栓形成,冠脉血管闭塞,是引起包括不稳定型心绞痛,急性心肌梗死和冠脉性猝死在内的急性冠脉综合征的病理基础。与防治血栓和再血管化相比,稳定斑块具有更大的临床价值。降脂药物、抗氧化剂、β受体阻滞剂、血管紧张素转换酶抑制剂具有肯定的稳定斑块作用。促进斑块基质合成,阻止降解,抑制斑块内炎症,阻断基质金属蛋白酶的合成和活化以及应用     

中性粒细胞与淋巴细胞比值在急性ST段抬高型心肌梗死中的应用

<正>急性ST段抬高型心肌梗死(STEMI)是急性心肌缺血性坏死,是在冠状动脉粥样硬化不稳定斑块病变的基础上继发斑块破裂、血栓形成,导致冠状动脉血管持续、完全阻塞,使相应的心肌严重而持久地急性缺血所致。炎症是触发急性心肌梗死的重要因素,炎症细胞里中性粒细胞、淋巴细胞不同的活化状     

基质金属蛋白酶与急性冠状动脉综合征的研究进展

随着对冠心病病例生理机制认识的不断深入，人们提出了急性冠状动脉综合征（acute coronary syndrome ACS）的新概念。ACS包括不稳定性心绞痛、急性心肌梗死和心脏性猝死。研究证实，冠状动脉粥样硬化斑块由稳定转为不稳定，继而破裂导致血栓形成是ACS最主要的发病机制。上述事件的发生，多数是由于狭窄并不十分严重的动脉粥样硬化斑块破裂、继发血栓形成造成的，虽然通过冠状动脉血运重建可纠正严重狭窄，但并不能改变动脉粥样硬化的生物学过程，斑块不稳定的问题仍然存在。因此，研究动脉粥样斑块破裂的机理，及寻找稳定斑块的有效治疗措施具有重要的临床意义。本文仅就基质金属蛋白酶与急性冠状动脉综合征的发病机制做一综述。     

不稳定型心绞痛的发病机制和治疗进展

不稳定型心绞痛型（ＵＡ）的临床不稳定性主要取决于其冠状动脉局部病变本身的不稳定。斑块破裂、炎症触发及发展、血栓形成、血管收缩与粥样斑块固定狭窄的程度及侧支循环状况的共同参与决定了ＵＡ的发生、发展。新的治疗目标是稳定活动的斑块，更为有效的抗血栓和抗血小板药物，减少缺血及再灌注心肌损伤，阻止动脉粥样硬化的发展。本文就此进展作一简述，特别对溶栓治疗不适于ＵＡ的机制作一阐述。１　发病机制１．１　斑块破裂〔１〕斑块表面突然破裂，血栓形成是ＵＡ的主要原因。决定斑块破裂的主要因素在于斑块的组成和脆性，而不是狭…     

稳定斑块——治疗急性冠状动脉综合征的新策略

急性冠状动脉综合征主要由于不稳定的冠状动脉粥样硬化斑块受侵蚀或破裂继发血栓引起。不稳定斑块的特征包括巨大的脂核、炎症细胞和炎症介质的增多以及较薄的纤维帽。对此进行干预可望达到稳定斑块的目的,从而给急性冠状动脉综合征的防治带来新的前景。     

预测颈动脉粥样硬化易损斑块的新型生物标志物研究进展

易损斑块是指动脉壁内稳定性差的斑块,其易破裂、脱落,导致原位血栓或多发微栓子形成。颈动脉粥样硬化易损斑块是缺血性脑卒中的主要致病机制,颈动脉斑块易损性增加脑缺血事件的发生。因此,早期鉴别易损斑块,对干预脑卒中高危因素、改善脑卒中预后具有重要意义。除各类影像技术外,循环生物标志物为识别颈动脉易损斑块提供了辅助手段。本综述回顾以往研究,讨论能够识别颈动脉易损斑块的新型生物标志物。     

微钙化与易损斑块相关性的研究进展

不良心血管事件（ACE）的发生,大部分是在动脉管腔轻至中度狭窄的基础上,由易损斑块破裂或侵蚀以及血栓形成所致。现代医学对冠状动脉粥样化性疾病的研究,已从以往仅关注管腔狭窄的程度向关注斑块的易损性转变。因此,探索易损斑块破裂的机制,早期识别易损斑块,预防ACE的发生成为心血管疾病研究领域的热点之一。近年来,大量研究发现动脉粥样硬化（AS）斑块内微钙化（microcalcifications,μCalcs）的出现与斑块的易损性关系密切,由此推测μCalcs可能是引起斑块破裂的一个重要因素。本文对AS斑块内μCalcs与易损斑块的相关性作一综述。     

Atherothrombosis: plaque instability and thrombogenesis

Hemostasis involves a carefully regulated balance between circulating and endothelium-derived prothrombotic and antithrombotic factors. The unstable or vulnerable plaque facilitates thrombosis, clinically manifest as an acute coronary syndrome (ACS), by creating an environment that favors thrombus formation over prevention of lysis. Endothelial cell dysfunction is integral to both the development of the atherosclerotic lesion as well as its destabilization. The transformation of a stable plaque to an unstable one involves complex interactions among T lymphocytes, macrophages, endothelial cells, and smooth muscle cells. Degradation of the fibrous cap of the atherosclerotic lesion as well as the overexpression of prothrombotic and underexpression of antithrombotic factors by cells within the plaque precede thrombus formation. Accordingly, pharmacological interventions for the treatment of ACS are directed against the initiation and propagation of thrombosis, as well as toward improvement of endothelial function.     

Inflammation and plaque vulnerability

Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a breakdown of integrity at the arterial surface triggers the formation of a thrombus. By occluding the lumen, the thrombus or emboli detaching from it elicits ischaemic symptoms that may be life‐threatening. Two types of surface damage can cause atherothrombosis: plaque rupture and endothelial erosion. Plaque rupture is thought to be caused by loss of mechanical stability, often due to reduced tensile strength of the collagen cap surrounding the plaque. Therefore, plaques with reduced collagen content are thought to be more vulnerable than those with a thick collagen cap. Endothelial erosion, on the other hand, may occur after injurious insults to the endothelium instigated by metabolic disturbance or immune insults. This review discusses the molecular mechanisms involved in plaque vulnerability and the development of atherothrombosis.     

Atherosclerotic plaque biomarkers: beyond the horizon of the vulnerable plaque

Cardiovascular disease (CVD) is the number one cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic inflammatory disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability, leading to thrombus formation and cardiovascular events. Due to the burden of cardiovascular disease, identification of patients at risk for cardiovascular events and treatment stratification is needed. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Imaging modalities have focused on the characteristics of the vulnerable plaque. However, it has become evident that not all so-called vulnerable plaques lead to rupture and subsequent thrombosis. The latter obviously limits the positive predictive value for imaging assessment of plaques and patients at risk. Serum biomarkers have also been studied extensively, but have very limited application in a clinical setting for risk stratification. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future cardiovascular events, also in other territories of the vascular tree. Results look promising and plaque markers can be used to develop imaging modalities to identify patients at risk, or to monitor treatment effect. Plaque biomarker studies do not challenge the definition of the vulnerable plaque, but use its concept in favor of prediction improvement for vascular patients.     

Markers of hemostasis and systemic inflammation in heart disease and atherosclerosis in smokers

Smoking is a major cause of both chronic obstructive pulmonary disease (COPD) and coronary heart disease, the latter being more common in individuals with COPD. Acute coronary events are usually caused by the development of a platelet-rich thrombus associated with atheromatous plaque rupture or erosion. Levels of systemic biomarkers of inflammation and hemostasis may reflect the presence of atherosclerosis and predisposition to thrombosis, and may allow identification of "vulnerable plaque" and "vulnerable blood" in "vulnerable patients." Hemostasis and inflammation, often viewed as separate processes, are integrated closely, and their response to smoking likely has contributed to the current coronary heart disease epidemic. Coagulation is initiated after exposure of blood to tissue factor present in atheromatous plaques. Fibrinogen and other hemostatic factors important in thrombus formation are influenced by inflammatory stimuli, possibly reflecting both vascular and systemic inflammation. Smokers who develop COPD may have higher basal levels of inflammatory markers, such as fibrinogen, due to lung damage, and respiratory infections to which they are prone may further increase levels, predisposing smokers to coronary events. In summary, smoking predisposes to coronary heart disease and the mechanisms may involve proinflammatory and procoagulant changes. These changes may be more marked in smokers with COPD.     

Photodynamic therapy for the treatment of atherosclerotic plaque: Lost in translation?

Acute coronary syndrome is a life‐threatening condition of utmost clinical importance, which, despite recent progress in the field, is still associated with high morbidity and mortality. Acute coronary syndrome results from a rupture or erosion of vulnerable atherosclerotic plaque with secondary platelet activation and thrombus formation, which leads to partial or complete luminal obstruction of a coronary artery. During the last decade, scientific evidence demonstrated that when an acute coronary event occurs, several nonculprit plaques are in a “vulnerable” state. Among the promising approaches, several investigations provided evidence of photodynamic therapy (PDT)‐induced stabilization and regression of atherosclerotic plaque. Significant development of PDT strategies improved its therapeutic outcome. This review addresses PDT's pertinence and major problems/challenges toward its translation to a clinical reality.     

Plaque disruption and the acute coronary syndromes of unstable angina and myocardial infarction: if the substrate is similar, why is the clinical presentation different?

In a majority of instances, both unstable angina and acute myocardial infarction occur secondary to plaque disruption and thrombus formation. Although the pathogenetic substrates are similar the clinical presentations are quite different. It is hypothesized in this editorial review that the amount of acute thrombus formation and specifically fibrin deposition is greater in myocardial infarction than in unstable angina. Both angiographic studies and studies analyzing the response to thrombolytic agents suggest more thrombus in myocardial infarction than in unstable angina. These data have recently been substantiated by angioscopic observations in these acute syndromes suggesting that more platelet-rich (whitish) thrombus occurs in unstable angina and more red thrombus in myocardial infarction. The red thrombus presumably would be more responsive to thrombolytic agents. Furthermore, it is proposed that these differences between syndromes in acute thrombus formation can be explained by the interplay of vessel wall injury, coagulation variables or stasis of blood flow occurring at or after the time of presentation. Therefore, acute myocardial infarction is associated with occlusive, fibrin-rich thrombus, whereas in unstable angina, the thrombus is nonocclusive, mural and possibly more platelet-rich. However, the clinical syndrome that ultimately develops after plaque disruption is dependent not only on the amount of acute thrombus formation but on the net result of all factors that influence the balance between coronary blood supply and myocardial oxygen demand.     

Thrombosis formation on atherosclerotic lesions and plaque rupture

Atherosclerosis is a silent chronic vascular pathology that is the cause of the majority of cardiovascular ischaemic events. The evolution of vascular disease involves a combination of endothelial dysfunction, extensive lipid deposition in the intima, exacerbated innate and adaptive immune responses, proliferation of vascular smooth muscle cells and remodelling of the extracellular matrix, resulting in the formation of an atherosclerotic plaque. High‐risk plaques have a large acellular lipid‐rich necrotic core with an overlying thin fibrous cap infiltrated by inflammatory cells and diffuse calcification. The formation of new fragile and leaky vessels that invade the expanding intima contributes to enlarge the necrotic core increasing the vulnerability of the plaque. In addition, biomechanical, haemodynamic and physical factors contribute to plaque destabilization. Upon erosion or rupture, these high‐risk lipid‐rich vulnerable plaques expose vascular structures or necrotic core components to the circulation, which causes the activation of tissue factor and the subsequent formation of a fibrin monolayer (coagulation cascade) and, concomitantly, the recruitment of circulating platelets and inflammatory cells. The interaction between exposed atherosclerotic plaque components, platelet receptors and coagulation factors eventually leads to platelet activation, aggregation and the subsequent formation of a superimposed thrombus (i.e. atherothrombosis) which may compromise the arterial lumen leading to the presentation of acute ischaemic syndromes. In this review, we will describe the progression of the atherosclerotic lesion along with the main morphological characteristics that predispose to plaque rupture, and discuss the multifaceted mechanisms that drive platelet activation and subsequent thrombus formation. Finally, we will consider the current scientific challenges and future research directions.