虚拟组织学血管内超声检测冠状动脉易损斑块的临床应用进展

<正>动脉粥样硬化易损斑块(vulnerable plaque)破裂和继发血栓形成是导致急性心血管事件的主要原因。易损斑块具有薄纤维帽、大脂质核心及包含大量巨噬细胞在内的炎症细胞浸润的主要病理特征,即薄纤维帽粥样斑块(thin-cap fibroatheroma,TCFA),其易于破裂。易损斑块的早期识别和干预对于急性心血管事件的预防具有十分重要的意义。虚拟组织学血管内超声(virtual histology intravascular ultra-     

易损斑块动物模型研究进展

易损斑块在急性冠状动脉综合征的发生发展中起着重要作用,减少易损斑块的破裂对降低不良心血管事件有重大意义。近年来,易损斑块的研究成为心血管领域的热点,但由于动物基因组和人类基因组的差异,以及斑块形成的病理生理过程不同,目前动物模型所形成的斑块与人类易损斑块还有很大差异。因此,建立与人类动脉粥样硬化斑块相似的动物模型成为目前亟待解决的难题。     

微观结构在易损斑块进展中的作用

急性冠状动脉综合征常常导致严重的心血管事件,而冠状动脉粥样硬化斑块破裂是绝大多数急性冠状动脉综合征发生的原因,因此检测高破裂风险的易损斑块,对筛选和干预急性冠状动脉综合征具有重要意义。随着研究的不断进展,易损斑块内的一些微观结构如斑块内新生血管、微小钙化、胆固醇结晶,在易损斑块的进展中起到重要的作用。因此,本文以易损斑块内最常见的3种微观结构为重点,综述斑块内微观结构在易损斑块进展中的作用。     

冠脉造影、血管内超声成像及虚拟组织学检测易损斑块的研究进展

全球每年约有2 000多万人出现突发性心脏事件,包括急性冠状动脉综合征(ACS)和(或)心脏性猝死。ACS的主要启动机制是罪犯血管动脉粥样斑块破裂和伴随的血栓形成。近几年来提出"易损斑块(vulnerable plaque)"这一概念,即将导致急性心血管事件的斑块统一命名为易损斑块。     

易损斑块的诊治进展

粥样斑块破裂被视为ACS发生中最重要的始动环节,粥样斑块破裂取决于斑块的易损性。易损斑块的早期识别诊断和正确治疗,对于降低急性心血管事件死亡率的意义尤为重大。本文对易损斑块的诊断和全面治疗予以综述。     

易损斑块的影像诊断研究新进展

易损斑块是一种不稳定、易破裂、具有血栓形成倾向的动脉血管病变。它具有特征性的薄弱纤维帽与较大脂质核心,是引发一系列不良心血管事件、威胁患者生命的罪犯斑块。新兴数据表明,不良心血管事件的发生主要由传统血管造影术无法检出的不稳定斑块破裂引起。因此,敏感、特异地识别易损斑块对于降低心血管病患者急性心血管事件发生率、改善患者治疗及预后具有重要意义。近年来,各类侵入性及非侵入性影像学诊断方法的发展使诊断易损斑块成为了可能。综述阐述了易损斑块的基本概念及病理特点,总结了近年来各类影像学诊断方法的临床应用价值及其主要的局限性和前景。     

冠状动脉易损斑块的治疗进展

动脉粥样硬化是全身性、慢性炎症性疾病,以局部突出表现为主。冠状动脉粥样硬化是冠状动脉性心脏病最主要病因,冠状动脉性心脏病患者发生急性冠状动脉事件的后果十分严重,常危及生命,而易损斑块是导致急性冠状动脉综合征主要罪犯病变。因此,对易损斑块的早期识别以及积极干预,对于预防急性心血管事件的发生至关重要,具有非常重要的临床意义。现就冠状动脉易损斑块的治疗最新进展做一综述。     

光学相干断层成像评价易损斑块的应用进展

急性心血管事件是致死率极高的疾病,粥样斑块破裂后血栓形成被认为是许多急性心血管事件的直接原因。在过去几十年里,光学相干断层成像(OCT)逐渐被运用于准确识别易损斑块,OCT是一种利用光学原理的血管内成像新技术,具有高分辨率及良好的组织相关性。现就将OCT评价易损斑块的应用进展做一综述。     

虚拟组织学对急性冠状动脉综合征患者斑块评价研究进展

人们一直不断探索冠心病发生发展的病理机制,积极探索易损斑块、易损病变、易损患者的识别方法,减少心血管事件。血管内超声虚拟组织学是研究冠状动脉病变特征的简单有效的手段之一。近期对于急性冠状动脉综合征的血管内超声虚拟组织学研究显示薄帽纤维粥样硬化斑块与长期的不良心血管事件相关。冠状动脉不同部位发生易损斑块的概率不同。吸烟、高胆固醇血症与斑块不稳定性相关。他汀类药物可减少斑块容积,但是对斑块成分的影响仍不明确。目前仍无可靠的血清学标志物显示冠状动脉斑块的易损性。     

血管内超声对急性冠状动脉综合征的认识

斑块破裂基础上血栓形成是急性冠状动脉(冠脉)综合征发生的主要病理机制。血管内超声在心导管室中应用越来越广泛,它能够在体观察斑块组成以及识别血栓和斑块破裂,有助于加深对急性冠脉综合征的认识。但是,心血管事件发生之前常常没有先兆症状,如果我们能够在急性冠脉事件发生之前检出易损斑块,并进行临床干预使之稳定,不良心血管事件的发生将大大减少。血管内超声下,含有无回声区脂质软斑块、薄纤维帽和正性重构被认为斑块易损的标志。当然,我们不仅要关注于局部病变性质的判断和处理,而且要着眼于整个冠状动脉和相关的系统因素。     

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。     

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.     

From vulnerable plaque to vulnerable patient: the search for biomarkers of plaque destabilization

There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Ideally, increasing knowledge of the mechanisms of atherosclerotic plaque destabilization should be translated in clinical practice. Currently, the following commonly followed strategies can be identified with the objective to detect either the local vulnerable plaque that is prone to rupture and gives rise to a thrombotic occlusion, or the systemic vulnerable patient, who has a high probability to suffer from an adverse clinical event. On the one hand, studies are ongoing to determine local atherosclerotic plaque characteristics to predict future local plaque rupture and subsequent vascular thrombosis. Newly developed imaging modalities are being developed and validated to detect these plaques in vivo. On the other hand, systemic approaches are pursued to discover serum biomarkers that are applicable to define patients at risk for future cardiovascular events. We propose a third original approach that is optional but yet unexplored, that is, to use local plaque characteristics as a biomarker not just for local plaque destabilization but for future cardiovascular events due to plaque progression in any vascular system. This review aims to provide an overview of the current standings of the identification of the vulnerable plaque and the vulnerable patient.     

冠状动脉易损斑块相关炎性因子的研究进展

炎症在动脉粥样硬化(AS)中扮演重要的角色.炎症贯穿于疾病发生、发展的各个阶段,包括易损粥样斑块形成和最终的破裂.其过程涉及许多炎性细胞,如单核细胞源性巨噬细胞、T淋巴细胞及其合成和分泌的细胞因子、趋化因子和酶.这些炎性因子导致内皮细胞活化,平滑肌细胞增殖,纤维帽基质的降解而形成易损斑块.这些有关炎性因子通过各种方法 可从外周血检测到,且循环血液中的炎症因子浓度与将来的心血管事件的发生密切相关.现将易损和破裂斑块的生物标记物的最新进展进行综述.     

Melatonin stabilizes rupture‐prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORα‐dependent manner

Rupture of vulnerable plaques is the main trigger of acute cardio‐cerebral vascular events, but mechanisms responsible for transforming a stable atherosclerotic into a vulnerable plaque remain largely unknown. Melatonin, an indoleamine hormone secreted by the pineal gland, plays pleiotropic roles in the cardiovascular system; however, the effect of melatonin on vulnerable plaque rupture and its underlying mechanisms remains unknown. Here, we generated a rupture‐prone vulnerable carotid plaque model induced by endogenous renovascular hypertension combined with low shear stress in hypercholesterolemic ApoE^?/? mice. Melatonin (10 mg/kg/d by oral administration for 9 weeks) significantly prevented vulnerable plaque rupture, with lower incidence of intraplaque hemorrhage (42.9% vs. 9.5%, P = 0.014) and of spontaneous plaque rupture with intraluminal thrombus formation (38.1% vs. 9.5%, P = 0.029). Mechanistic studies indicated that melatonin ameliorated intraplaque inflammation by suppressing the differentiation of intraplaque macrophages toward the proinflammatory M1 phenotype, and circadian nuclear receptor retinoid acid receptor‐related orphan receptor‐α (RORα) mediated melatonin‐exerted vasoprotection against vulnerable plaque instability and intraplaque macrophage polarization. Further analysis in human monocyte‐derived macrophages confirmed the role of melatonin in regulating macrophage polarization by regulating the AMPKα‐STATs pathway in a RORα‐dependent manner. In summary, our data provided the first evidence that melatonin‐RORα axis acts as a novel endogenous protective signaling pathway in the vasculature, regulates intraplaque inflammation, and stabilizes rupture‐prone vulnerable plaques.     

Atherosclerotic expansive remodeled plaques: a wolf in sheep's clothing

Geometric arterial remodeling is an important determinant of luminal narrowing in atherosclerotic disease. Expansive remodeling retards while constrictive remodeling accelerates luminal narrowing by plaque formation. Cross-sectional as well as follow-up studies revealed that expansive remodeling is associated with adverse cardiovascular events and a vulnerable plaque phenotype. Although the relation between expansive remodeling and plaque vulnerability is associative rather than causal, expansively remodeled plaques should be considered as a wolf in sheep's clothes. Further understanding of the processes that regulate arterial remodeling and plaque rupture may lead to new strategies to responsibly manipulate these processes for the benefit of patient outcomes.     

The vulnerable plaque: Current concepts and future perspectives on coronary morphology,composition and wall stress imaging

Cardiovascular imaging plays an important role in the identification and characterization of the vulnerable plaque. A major goal is the ability to identify individuals at risk of plaque rupture and developing an acute coronary syndrome. Early recognition of rupture‐prone atherosclerotic plaques may lead to the development of pharmacologic and interventional strategies to reduce acute coronary events.We review state‐of‐the‐art cardiovascular imaging for identification of the vulnerable plaque. There is ample evidence of a close relationship between plaque morphology and patient outcome, but molecular imaging can add significant information on tissue characterization, inflammation and subclinical thrombosis. Additionally, identifying arterial wall exposed to high shear stress may further identify rupture‐prone arterial segments. These new modalities may help reduce the individual, social and economic burden of cardiovascular disease.     

Where is the trace? Molecular imaging of vulnerable atherosclerotic plaques

Serious cardiovascular events frequently arise from rupture of vulnerable atherosclerotic plaques. Not infrequently, these plaques are clinically silent and suddenly cause acute complications such as myocardial infarction, which in a high percentage are fatal. Thus, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in clinical medicine. This review highlights noninvasive scintigraphic techniques, which use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing their biological activity. One major principle is the molecular imaging of inflammation with radionuclide tracers, including detection of metabolic activity, chemotaxis, cell recruitment, and lipoprotein enrichment. Additional studies focus on visualization of apoptosis, angiogenesis, or proteolysis. A central feature of plaque vulnerability is its thrombogenicity. Therefore, detection of thrombogenic plaques is another promising principle of molecular imaging. If a reliable protocol to image vulnerable plaques, which are prone to rupture, can be established and introduced into clinical practice, the required measures such as atheroprotective medication or revascularization could be undertaken to prevent serious cardiovascular events.     

Detecting the vulnerable plaque in patients

Atherosclerosis is a systemic condition that eventually evolves into vulnerable plaques and cardiovascular events. Pathology studies reveal that rupture‐prone atherosclerotic plaques have a distinct morphology, namely a thin, inflamed fibrous cap covering a large lipidic and necrotic core. With the fast development of imaging techniques in the last decades, detecting vulnerable plaques thereby identifying individuals at high risk for cardiovascular events has become of major interest. Yet, in current clinical practice, there is no routine use of any vascular imaging modality to assess plaque characteristics as each unique technique has its pros and cons. This review describes the techniques that may evolve into screening tool for the detection of the vulnerable plaque. Finally, it seems that plaque morphology has been changing in the last decades leading to a higher prevalence of ‘stable’ atherosclerotic plaques, possibly due to the implementation of primary prevention strategies or other approaches. Therefore, the nomenclature of vulnerable plaque lesions should be very carefully defined in all studies.