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。     

不稳定性冠状动脉粥样硬化斑块的研究进展

冠状动脉粥样硬化斑块的不稳定性是引发急性冠脉综合征 (包括不稳定型心绞痛、急性心肌梗死、心性猝死 )的主要原因 ,也是引起冠心病死亡的主要原因。大量研究表明 ,约 6 0 %～ 70 %的急性冠脉综合征是由于轻、中度狭窄的斑块破裂 ,继发血栓形成所致。冠状动脉血运重建虽可减轻冠脉狭窄程度 ,但与药物治疗相比 ,长期随访未明显减少急性冠脉事件发生率 ,主要原因是斑块的不稳定问题尚未解决。因此 ,认识不稳定斑块的内在特性、破裂机制、识别方法 ,探讨稳定斑块的方法具有重要的临床意义。　　动脉粥样硬化斑块的结构及其不稳定的内在特征1.…     

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。     

炎症与急性冠状动脉综合征

冠状动脉不稳定性粥样斑块的破裂、表面破损或裂隙 ,随后继发的血小板聚集和血栓形成 ,引起冠状动脉急性完全或不完全堵塞 ,是导致包括不稳定型心绞痛 (UA)、急性心肌梗塞 (AMI)和心源性猝死的急性冠状动脉综合征 (Acutecoronarysyndromes,ACS)的主要病理机制。不稳定粥样斑块的标志是斑块内脂质丰富、炎症反应活跃、胶原与血管平滑肌细胞少 ,且纤维帽薄 ,容易破裂[1 ] 。目前认为 ,炎症反应在粥样斑块的不稳定性和破裂中起重要作用。因此 ,认识炎症与ACS的关系 ,对预防、诊断和治疗ACS非常重要。1　炎症反应参与急性冠状动脉综合征的…     

粥样斑块破裂的病理生理学

几种血管放射检查和形态学研究已经揭示尽管冠状动脉狭窄的原因是多样的,但90%以上是动脉粥样硬化。阻塞性冠状动脉疾病的主要损害是动脉粥样硬化斑块的破裂损伤,发生在动脉硬化部位表面损伤可发生内皮细胞剥蚀,而纵深的损伤可发现一个从腔内到斑块组织延伸的裂缝,斑块的裂缝和破裂可引起急性缺血性冠脉综合征(acuteischemiccoronarysyn-drome;AICS)[1]。本文对影响粥样斑块破裂的因素及其病理生理学内容综述如下:1　粥样硬化斑块稳定性的影响因素一般认为,粥样斑块是否稳定(或易于破裂)与下述因素有关。1.1　斑块内核的大小[2]:粥样斑块…     

冠状动脉粥样斑块的治疗现状与进展

冠状动脉粥样斑块是冠状动脉粥样硬化性心脏病的基本病理改变，斑块的破裂可以导致急性冠脉综合征。如何干预动脉粥样斑块是目前的研究热点，大量研究已证实，药物治疗、内皮祖细胞移植、生活方式干预等方法可以早期干预动脉粥样斑块。本文将从以上方面介绍冠状动脉粥样斑块的治疗方法研究现状及相关机制。     

妊娠相关血浆蛋白A在动脉粥样硬化斑块的表达

目的研究妊娠相关血浆蛋白A(PAPP-A)在破裂斑块、不稳定斑块与稳定斑块中的表达、分布特点,探讨其在斑块破裂中的作用。方法对51例有明确冠心病病史的死亡病例分离冠状动脉组织并切片,从中选取破裂斑块、不稳定斑块(未破裂)和稳定斑块各15块,应用免疫组织化学方法进行PAPP-A染色。结果15块破裂斑块中有12例PAPP-A染色阳性,而所有不稳定斑块与稳定斑块PAPP-A染色均为阴性。结论PAPP-A与动脉粥样斑块的破裂密切相关,可能对急性冠状动脉综合征的诊断、危险分层及病情监测具有重要价值。     

冠状动脉高血栓负荷病变的治疗策略及展望

正急性冠状动脉综合征(acute coronary syndrome,ACS)是一类严重的心血管疾病,多发生在冠状动脉粥样硬化斑块狭窄的基础上,不稳定斑块糜烂、破裂继发血栓形成,从而阻塞冠状动脉内血流,导致相应供血区域心肌出现缺     

不稳定斑块、炎症与急性冠状动脉综合征

急性冠状动脉综合征 (ACS)是一组由于冠状动脉斑块破裂致血管严重狭窄或闭塞而发生心肌缺血和 (或 )局部坏死的综合征 ,临床表现为不稳定型心绞痛 (U AP)、非 Q波及 Q波心肌梗死 (MI)和猝死。近来研究表明 ,不稳定斑块破裂是导致 ACS的主要原因 ,而炎症与不稳定斑块的发生、发展及破裂有极重要的联系。1　不稳定斑块与 ACS冠心病的病理基础是冠状动脉粥样硬化。人们最初认为 ,冠状动脉粥样斑块慢性进展使管腔严重狭窄是出现 ACS临床表现的主要原因。随着冠心病介入技术的开展 ,越来越多的证据发现 ACS患者冠状动脉的固定狭窄程度并…     

麝香保心丸抑制炎症反应在冠心病治疗中的作用

近年来的研究证实冠状动脉粥样硬化斑块破裂是急性冠脉综合征（ACS）的主要原因，而其中炎症反应使斑块趋于不稳定状态，易于发生斑块的破裂，促进血栓形成和血管闭塞，因此发现和治疗不稳定斑块具有重要意义。目前，人们公认的识别冠状动脉粥样硬化斑块稳定性的检测手段血管内超声和血管内镜，由于其价格昂贵和操作技术复杂而不能广泛开展。     

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.     

Plaque disruption and thrombosis: potential role of inflammation and infection

Acute coronary syndromes (unstable angina, acute myocardial infarction, and ischemic sudden death) result from coronary thrombosis superimposed on an atherosclerotic plaque. Thrombosis is generally a consequence of disruption of the atherosclerotic plaque in the form of a fissure/rupture in the fibrous cap overlying a lipid-rich pool or superficial endothelial erosion covering a smooth muscle and proteoglycan-rich matrix with or without a lipid-core. Approximately 2/3 of acute coronary syndromes evolve from atherosclerotic plaques that are minimally or mildly obstructive of the lumen before the acute event. Inflammation with accumulation of activated mononuclear cells may play a potential role in plaque disruption through the elaboration of proteases, such as matrix degrading neutral metalloproteinases and other proteases, inhibition of function and/or survival, or promotion of apoptosis of matrix synthesizing smooth muscle cells. Inflammation may also contribute to thrombosis after plaque disruption by providing a source for tissue factor in the plaque. Inflammation in the plaque may result from accumulation of modified lipids, oxidant and hemodynamic stress, and infectious agents, such as Chlamydia pneumoniae or pro-inflammatory triggers from distant sites of infection and inflammation (eg, chronic gingivitis and chronic bronchitis). Improved insights into the pathophysiology of plaque disruption and thrombosis are likely to provide new and improved methods of stabilizing atherosclerotic disease process.     

The role of plaque rupture and thrombosis in coronary artery disease

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized world. The progression of atherosclerotic plaques in the coronary circulation is dependent on several risk factors. It is now clear that plaque composition is a major determinant of the risk of subsequent plaque rupture and superimposed thrombosis. The vulnerability of plaques to rupture is further determined by extrinsic triggering factors. Following rupture, the fatty core of the plaque and its high content of tissue factor provide a powerful substrate for the activation of the coagulation cascade. Plaque rupture can be clinically silent or cause symptoms of ischaemia depending on thrombus burden and the degree of vessel occlusion. In addition, plaque rupture and subsequent healing is recognized to be a major cause of further rapid plaque progression. This review looks at the mechanisms underlying the development and progression of atherosclerotic plaques, factors leading to plaque rupture and subsequent thrombosis and their clinical consequences. Finally, we speculate on targets for future research.     

In-vivo prediction of human coronary plaque rupture location using intravascular ultrasound and the finite element method.

BACKGROUND: Spontaneous rupture of atherosclerotic plaques is known to be involved in the mechanism leading to acute coronary syndromes. Means to detect plaques prone to rupture and predict rupture location would then be very valuable for clinical diagnosis. DESIGN: In this study, finite element (FE) analysis based on intravascular ultrasound (IVUS) images of atherosclerotic arteries was used to predict in-vivo plaque rupture locations. In four patients with coronary artery diseases, IVUS images were recorded before and after balloon angioplasty. Pre-angioplasty images were recorded after injection of ATP. This caused a brief drop of arterial blood pressure down to values of about 20 mmHg, and thus allowed the recording of the unloaded configurations of arteries used to initiate FE analysis. Plaque rupture was triggered by balloon inflation (coronary angioplasty). FE simulations were performed under physiological loading conditions. Stress distributions within the plaque and the arterial wall were determined. The corresponding stress maps are presented. RESULTS: Circumferential tensile peak stress areas were compared with plaque rupture locations on postangioplasty IVUS images. They were found to coincide in all four studied cases. CONCLUSION: Our results agreed with those reported in previous studies based on ex-vivo postnecropsic data and showed the feasibility of in-vivo prediction of atherosclerotic plaque rupture location.     

Pathophysiology and clinical significance of atherosclerotic plaque rupture.

Atherosclerotic plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes. These syndromes include unstable angina, non-Q-wave myocardial infarction (MI) and Q-wave MI. In addition, many cases of sudden cardiac death may be attributable to atherosclerotic plaque disruption and its immediate complications. Our understanding of the atherosclerotic process and the pathophysiology of plaque disruption has advanced remarkably. Despite these advances, event rates after acute coronary syndromes remain unacceptably high. This review will focus on the pathophysiology underlying atherosclerotic plaque development, the sequellae of coronary plaque rupture, and current therapies designed to treat the acute coronary syndromes. It is hoped that as our understanding of the atherosclerotic plaque improves, treatment strategies for the acute coronary syndromes will advance.     

Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse

The rupture of an atherosclerotic plaque is the main underlying cause of coronary artery thrombotic occlusion and subsequent myocardial infarction, but research into the causes and treatment of plaque rupture is hampered by the lack of a suitable animal model. Although complex atherosclerotic plaques can be induced in a number of experimental animal systems, in none of these is plaque rupture an established feature. We have surveyed branch points in the carotid arteries and aortas of apolipoprotein E knockout mice fed a diet supplemented with 21% lard and 0.15% cholesterol for up to 14 months. Six male and five female mice were used. Four of the male mice and four of the female mice died, after 46+/-3 weeks of feeding (range 37-59 weeks). Lumenal thrombus associated with atherosclerotic plaque rupture was observed in three male and all four female mice. In six of these seven mice, an atherosclerotic plaque rupture was found where the brachiocephalic artery branches into the right common carotid and right subclavian arteries. The ruptures were characterised by fragmentation and loss of elastin in the fibrous caps of relatively small and lipid-rich plaques overlying large complex lesions, with intraplaque haemorrhage. Immunocytochemical analysis revealed loss of smooth muscle cells from ruptured caps. These data suggest that long-term fat-feeding of apolipoprotein E knockout mice is a useful and reproducible model of atherosclerotic plaque rupture, and that these ruptures occur predominantly in the brachiocephalic artery.     

Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis—often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.     

Rupture of the atherosclerotic plaque: does a good animal model exist?

By its very nature, rupture of the atherosclerotic plaque is difficult to study directly in humans. A good animal model would help us not only to understand how rupture occurs but also to design and test treatments to prevent it from happening. However, several difficulties surround existing models of plaque rupture, including the need for radical interventions to produce the rupture, lack of direct evidence of rupture per se, and absence of convincing evidence of platelet- and fibrin-rich thrombus at the rupture site. At the present time, attention should therefore focus on the processes of plaque breakdown and thrombus formation in humans, whereas the use of animal models should probably be reserved for studying the function of particular genes and for investigating isolated features of plaques, such as the relationship between cap thickness and plaque stability.     

新生滋养血管在动脉粥样硬化形成中的作用及临床意义

动脉粥样硬化(As)病变的主要临床危险性在于斑块的不稳定性、易损性。斑块内新生滋养血管(VV)具有结构缺陷,其脆性大、渗漏性高,容易破裂出血,促进炎症反应,也为血细胞及血液可溶性成分进入斑块提供通道,促进As斑块的形成,并且与斑块内出血、斑块破裂及临床心脑血管事件的发生密切相关。深入研究新生滋养血管的功能及关键信号途径在As中的作用,有望从根本上阻止稳定斑块发展为易损斑块,或者阻止不稳定斑块破裂及其并发症的发生。     

颈动脉粥样硬化斑块内新生血管的研究现状及进展

颈动脉粥样硬化斑块破裂是导致脑卒中的重要原因之一,大量研究证实颈动脉斑块内新生血管是导致斑块内出血、斑块破裂的重要因素。炎症因子及各类细胞通过斑块内新生血管进入斑块,导致斑块稳定性破坏,但影响斑块内新生血管形成的重要相关因子和主要机制目前尚未完全明确,因此识别斑块内新生血管、探索斑块内新生血管形成的相关因子及机制是研究斑块内新生血管致斑块不稳定性的关键。抑制斑块内新生血管生成,可能成为防治颈动脉斑块破裂、降低脑栓塞事件发生的新策略。本综述旨在探讨颈动脉斑块内新生血管形成的相关因子、机制以及检测成像的最新研究进展,为动脉粥样硬化的诊疗提供支持。