载脂蛋白E基因敲除小鼠动脉粥样硬化斑块中血小板因子4和Toll样受体2的表达

目的观察高脂饲养的载脂蛋白E基因敲除小鼠动脉粥样硬化斑块表达Toll样受体2和血小板因子4的情况,探讨血小板因子4对内皮细胞Toll样受体2表达的影响。方法高脂饲料喂养载脂蛋白E基因敲除小鼠12周,建立动脉粥样硬化模型。安乐死处死动物,原位灌流固定,取主动脉于10%中性缓冲福尔马林中固定,石蜡包埋连续切片,HE染色观察动脉粥样硬化斑块形态,免疫组织化学检测斑块中Toll样受体2和血小板因子4的表达。结果载脂蛋白E基因敲除小鼠血脂水平明显增高,主动脉HE染色可见态动脉粥样硬化病变。在载脂蛋白E基因敲除小鼠主动脉富含脂质斑块中Toll样受体2表达上调,其中血管内皮细胞、巨噬细胞表达Toll样受体2明显增多。载脂蛋白E基因敲除小鼠主动脉斑块中也发现有血小板因子4表达,主要在内皮细胞和动脉粥样硬化斑块肩部。结论1.载脂蛋白E基因敲除小鼠粥样斑块中Toll样受体2表达上调,并且Toll样受体2主要表达在粥样斑块的内皮细胞和巨噬细胞上。2.载脂蛋白E基因敲除小鼠动脉粥样硬化斑块中可见血小板因子4表达。     

TLR2/4-IRF3信号通路调控胆固醇逆转运及其对动脉粥样硬化影响的研究进展

Toll样受体（toll like receptors,TLRs）是天然免疫系统识别病原微生物的主要受体,在天然免疫反应中具有重要的作用,TLR2／4-IRF3信号通路对胆固醇逆转运的调控能对动脉粥样硬化易损斑块产生影响。本文就TLR2／4-IRF3信号通路如何调控胆固醇逆转运从而影响动脉粥样硬化的发生发展作一综述。     

凝集素样氧化型低密度脂蛋白受体1与动脉粥样硬化易损斑块

凝集素样氧化型低密度脂蛋白受体1是新发现的主要在血管内皮细胞表达的氧化型低密度脂蛋白受体,对动脉粥样硬化的发生发展有着重要意义。近年来,越来越多的研究显示凝集素样氧化型低密度脂蛋白受体1与动脉粥样硬化易损斑块之间存在重要联系。     

动脉粥样硬化易损斑块与TLR4/NF-κB信号通路关系的研究进展

Toll受体4（TLR4）能识别多种病原相关分子模式,并能促进白细胞浸润、脂质核心的形成、纤维帽变薄、血管新生等病理过程,在动脉粥样硬化易损斑块的发生发展中的作用极其重要。TLR4能激活核转录因子（NF-κB）和促炎性蛋白,进一步促进炎症反应的发生和动脉粥样斑块的不稳定性增加。本文总结近年有关动脉粥样硬化易损斑块与TLR4/NF-κB信号通路关系的研究进展。     

Toll样受体与动脉粥样硬化

动脉粥样硬化作为一种炎症性疾病,研究表明感染因子与动脉粥样硬化的发生与发展有关。Toll样受体是天然免疫系统识别病原微生物的主要受体．在天然免疫反应中具有重要的作用,近年来研究认为Toll样受体之一Toll样受体4与动脉粥样硬化的发生发展密切相关．其可能成为动脉粥样硬化防治的标靶．本文主要对Toll样受体4在动脉粥样硬化的发生发展中的作用作一综述．     

Toll样受体与动脉粥样硬化

固有免疫应答与动脉粥样硬化斑块形成有关。固有免疫识别中的模式识别受体 Toll样受体信号通路与动脉粥样硬化发病机理的关系,解释了针对外来病原体的非特异性防御以及内源性炎症分子导致动脉粥样硬化的可能机制。     

Toll样受体与动脉粥样硬化

固有免疫应答与动脉粥样硬化斑块形成有关.固有免疫识别中的模式识别受体Toll样受体信号通路与动脉粥样硬化发病机理的关系,解释了针对外来病原体的非特异性防御以及内源性炎症分子导致动脉粥样硬化的可能机制.     

脑心通胶囊对不稳定斑块兔TLR-2和TLR-4炎性信号转导因子的影响

目的探讨脑心通胶囊稳定易损斑块的机制。方法45只兔给予球囊损伤腹主动脉及高脂饲料喂养,12周末造模兔随机分为自然消退组、脑心通组和辛伐他汀组,每组15只。24周末在腹主动脉斑块处转染携带人野生型p53基因,2周后给予中国斑点蝰蛇毒(CRVV)和组胺触发斑块破裂。于26周末通过免疫组化、WesternBlotting及实时定量RT-PCR分析,检测用药后经p53基因转染处Toll样受体2(TLR-2)、Toll样受体4(TLR-4)和核转录因子κB(NF-κB)的表达。结果转染后动脉粥样硬化斑块处有大量TLR-2、TLR-4和NF-κB表达,尤其集中于内皮细胞和巨噬细胞及炎性细胞浸润处。三者在脑心通组和辛伐他汀组的表达较自然消退组显著降低。结论TLR-2、TLR-4的表达量可预测动脉粥样硬化(AS)斑块的进展,脑心通胶囊可通过降低TLR-2、TLR-4的过度表达而稳定斑块。     

Toll样受体与动脉粥样硬化

动脉粥样硬化是心脑血管疾病的病理基础,其发病机制备受关注但至今尚未阐明,包括天然免疫和获得性免疫在内的免疫机制在动脉粥样硬化中的作用不容忽视。Toll样受体是一类介导天然免疫的受体家族,近年来认为Toll样受体4与动脉粥样硬化的发生发展密切相关。现主要就Toll样受体的结构、分布及配体识别特点,特别是Toll样受体4与动脉粥样硬化的相关性研究作一综述。     

Toll样受体4在动脉粥样硬化中的作用研究进展

Toll样受体尤其是Toll样受体4作为介导天然免疫反应的一类跨膜受体蛋白在动脉粥样硬化进程中的作用日益引起关注,本文就其结构、配体及其在动脉粥样硬化各阶段作用及动脉粥样硬化免疫学治疗现状作一概述。     

Genotype association of C(-735)T polymorphism of the MMP-2 gene with the risk of carotid atherosclerosis-vulnerable plaque in the Han Chinese population

The aim of the current study was to explore the possible association of the polymorphism of C(-735)T in MMP-2 with the vulnerable plaque risk in ultrasound-confirmed carotid atherosclerosis cases. Serum MMP-2 levels were measured to investigate the relationship between the MMP-2 level and the genetic variability. The MMP-2 polymorphism was detected by PCR-RFLP in the 243 cases with stable plaque and 221 cases with vulnerable plaque. Serum MMP-2 levels were measured with ELISA. The results showed that MMP-2 was significantly higher in the cases with vulnerable plaque than in the cases with stable plaque. A statistical difference was found between the genotype distributions in the vulnerable plaque cases and that in the stable cases. T-allele frequency was also found to be over-represented in the stable plaque cases than in the vulnerable plaque cases, which might partially explain the observed difference in the serum MMP-2 levels in the different plaque cases. The current results also suggested that MMP-2 was a risk factor in the cases with vulnerable plaques, whereas TT genotype and T allele might be protective factors in the cases with vulnerable plaques.     

易损斑块对晚期药物支架贴壁不良影响的虚拟组织学血管内超声研究

目的:探讨基线斑块组织分型对药物支架(drug-eluting stent,DES)置入术后晚期支架贴壁不良(late stent malapposition,LSM)的影响。方法:入选不稳定性心绞痛患者112例,行冠状动脉原位病变药物支架置入及基线和随访,平均随访时间(11.5±1.7)个月,虚拟组织学血管内超声(VH-IVUS)检查,分为易损斑块组(n=38)和非易损斑块组(n=74)。结果:16例患者(14.3%)随访时发现LSM,易损斑块组明显多于非易损斑块组(28.9%vs.6.8%,P=0.001)。易损斑块组糖尿病(52.6%vs.28.4%,P=0.012),支架长度,坏死核心体积[(28.7±9.6)vs.(22.0±11.2)mm3,P=0.004]及其百分比[(25.7±6.6)vs.(21.5±6.6)%,P0.001]均明显高于非易损斑块组。多因素回归分析显示,易损斑块(OR=3.162,95%CI:1.052~11.278,P=0.001)和糖尿病(OR=1.145,95%CI:1.005~1.332,P=0.024)是LSM的独立预测因素。结论:易损斑块和糖尿病与不稳定心绞痛DES置入术后LSM形成有关。     

内皮祖细胞在动脉粥样硬化易损斑块中的作用

目的 动脉粥样硬化易损斑块是急性冠状动脉综合征和心脏缺血性猝死的重要病理基础.研究证实易损斑块表面大面积内皮细胞受损和血栓形成,内皮受损后可引起炎症因子瀑布样反应、单核细胞浸润和血管平滑肌细胞增生,进而促发动脉粥样硬化易损班块形成,故修复受损血管内皮、促使血管重新内皮化已经成为防止动脉粥样硬化的重要课题.近年研究认为,...     

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。     

冠状动脉CT成像与易损斑块

冠状动脉内斑块破裂或侵蚀所致的急性腔内血栓是急性冠状动脉综合征的主要原因。防止急性血栓形成成为了降低冠状动脉粥样硬化性心脏病病死率的唯一有效策略。斑块易破裂的冠状动脉病变与稳定斑块相比,存在不同的形态学改变。因此可以利用特殊的成像方法来识别这些易损斑块。亚毫米空间分辨率和图像质量优良的现代计算机断层扫描方法可以对冠状动脉斑块进行检测、分析和量化。斑块体积较大、低CT衰减、餐巾环征、正性重构以及点状钙化等与斑块容易破裂有密切关系。将冠状动脉斑块的形态学与功能特征等相结合,在未来有可能成为检测易损斑块的新方法。现将就多层螺旋CT与冠状动脉易损斑块的检测做一综述。     

Atherothrombosis and high-risk plaque: part I: evolving concepts.

Atherothrombosis is a complex disease in which cholesterol deposition, inflammation, and thrombus formation play a major role. Rupture of high-risk, vulnerable plaques is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. In addition to rupture, plaque erosion may also lead to occlusive thrombosis and acute coronary events. Atherothrombosis can be evaluated according to histologic criteria, most commonly categorized by the American Heart Association (AHA) classification. However, this classification does not include the thin cap fibroatheroma, the most common form of high-risk, vulnerable plaque. Furthermore, the AHA classification does not include plaque erosion. As a result, new classifications have emerged and are reviewed in this article. The disease is asymptomatic during a long period and dramatically changes its course when complicated by thrombosis. This is summarized in five phases, from early lesions to plaque rupture, followed by plaque healing and fibrocalcification. For the early phases, the role of endothelial dysfunction, cholesterol transport, high-density lipoprotein, and proteoglycans are discussed. Furthermore, the innate and adaptive immune response to autoantigens, the Toll-like receptors, and the mechanisms of calcification are carefully analyzed. For the advanced phases, the role of eccentric remodeling, vasa vasorum neovascularization, and mechanisms of plaque rupture are systematically evaluated. In the final thrombosis section, focal and circulating tissue factor associated with apoptotic macrophages and circulatory monocytes is examined, closing the link between inflammation, plaque rupture, and blood thrombogenicity.     

易损斑块的诊断进展

急性冠状动脉综合征患者具有较高的发病率,预后较差,而冠状动脉内易损斑块破裂伴随血栓形成是其主要原因.因此早期正确诊断易损斑块,对于急性冠脉综合征的防治具有重大意义.现就易损斑块的诊断进展作一综述.     

Atherothrombosis and high-risk plaque: part I: evolving concepts

Atherothrombosis is a complex disease in which cholesterol deposition, inflammation, and thrombus formation play a major role. Rupture of high-risk, vulnerable plaques is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. In addition to rupture, plaque erosion may also lead to occlusive thrombosis and acute coronary events. Atherothrombosis can be evaluated according to histologic criteria, most commonly categorized by the American Heart Association (AHA) classification. However, this classification does not include the thin cap fibroatheroma, the most common form of high-risk, vulnerable plaque. Furthermore, the AHA classification does not include plaque erosion. As a result, new classifications have emerged and are reviewed in this article. The disease is asymptomatic during a long period and dramatically changes its course when complicated by thrombosis. This is summarized in five phases, from early lesions to plaque rupture, followed by plaque healing and fibrocalcification. For the early phases, the role of endothelial dysfunction, cholesterol transport, high-density lipoprotein, and proteoglycans are discussed. Furthermore, the innate and adaptive immune response to autoantigens, the Toll-like receptors, and the mechanisms of calcification are carefully analyzed. For the advanced phases, the role of eccentric remodeling, vasa vasorum neovascularization, and mechanisms of plaque rupture are systematically evaluated. In the final thrombosis section, focal and circulating tissue factor associated with apoptotic macrophages and circulatory monocytes is examined, closing the link between inflammation, plaque rupture, and blood thrombogenicity.     

颈动脉粥样硬化易损斑块影像学诊断研究进展

缺血性脑卒中具有较高的发病率、致残率、死亡率及高复发率,颈动脉易损斑块是其主要原因。因此早期正确诊断易损斑块,对于急性脑卒中的防治具有重大意义。该文从超声、CT、MRI、脑血管造影等方面对易损斑块的诊断进展进行综述。     

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。