冠状动脉血栓形成的病理生理学——斑块破裂和斑块糜烂的作用

本文综述了冠状动脉粥样硬化血栓形成的病理生理学 ,斑块破裂和斑块糜烂在冠状动脉血栓形成中的作用 ,斑块破裂的机制和稳定斑块的治疗原则     

血管新生对动脉粥样硬化斑块稳定性影响的研究进展

斑块内血管新生由低氧和炎症等因素诱导形成,在动脉粥样硬化斑块的发生发展中发挥了重要作用。一方面通过加剧炎症反应和诱发斑块内出血,影响斑块的稳定性,从而诱发死亡率极高的急性冠状动脉综合征;另一方面可缓解斑块内低氧状态,减少细胞坏死,为斑块内有害物质的移出提供通道。抗血管生成治疗虽已投入临床应用,但在动脉粥样硬化方面进展甚小。本文就斑块内新生血管形成发生机制、血管新生对动脉粥样硬化斑块稳定性的影响及其相关临床应用进展作一综述。     

冠状动脉粥样硬化斑块稳定性鉴别的研究进展

不稳定性冠状动脉粥样硬化斑块是急性冠脉综合征(ACS)发生发展的主要原因。目前,迅速发展的影像学技术及各种炎症标志物的检测可较好的反映斑块的不稳定性,故其对于ACS及时正确诊断及治疗有重要意义。     

不同类型脑白质疏松与颈动脉粥样硬化斑块稳定性和血清脂蛋白相关磷脂酶A2的相关性

目的　探讨不同类型脑白质疏松（LA）患者颈动脉粥样硬化斑块稳定性及其与血清脂蛋白相关磷脂酶A2（Lp-PLA2）水平的关系。方法　将入组的LA患者根据头颅MRI表现分为脑室周围型组、皮质下型组和混合型组。应用颈动脉彩超检测颈动脉粥样硬化斑块并分为稳定性和不稳定性斑块,计算斑块积分。采用酸水解底物显色法测定血清Lp-PLA2水平。结果　三组患者在年龄、性别、血压、血糖、低密度脂蛋白和血尿酸水平方面差异无统计学意义（P＞0.05）;皮质下型组和混合型组斑块阳性率、不稳定性斑块积分较脑室周围型组显著增高（P＜0.01）;三组血清Lp-PLA2水平两两相比均有显著性差异（P＜0.05）,皮质下型组血清Lp-PLA2水平最高,脑室周围型组血清Lp-PLA2水平最低,皮质下型组血清Lp-PLA2水平与不稳定性斑块积分呈正相关（r＝0.270,P＜0.05）。结论　血清Lp-PLA2与颈动脉粥样硬化斑块的不稳定性存在一定的相关性,并通过炎症机制导致斑块破裂,在皮质下型LA的发生、发展中起重要作用。     

Inflammation and Plaque Vulnerability

Development of a thrombus at the site of an atherosclerotic plaque initiates abrupt arterial occlusion and is the proximate event responsible for the vast majority of acute ischemic syndromes. In nearly 75% of cases thrombus overlies a disrupted or ruptured plaque whereas the remainder of the thrombi overly an intact plaque with superficial endothelial erosion. Over the past several years, it has been recognized that plaque composition rather than plaque size or stenosis severity is important for plaque rupture and subsequent thrombosis. Ruptured plaques, and by inference, plaques prone to rupture, tend to be large in size with associated expansive arterial remodeling, thin fibrous cap with a thick or large necrotic lipid core with immuno-inflammatory cell infiltration in fibrous cap and adventitia and increased plaque neovascularity and intraplaque hemorrhage. The size of the necrotic lipid core and extent and location of plaque inflammation appear to be key factors in determining plaque instability. Inflammation and immune cell activation appears to play a key role in the loss of collagen in the fibrous cap, a prelude to fibrous cap rupture, through release of collagen degrading enzymes. Furthermore, inflammation may also play a key role in the death of collagen synthesizing smooth muscle cells which further contributes to loss of fibrous cap integrity. Inflammation also is likely a key player in the ensuing thrombosis that follows plaque disruption through the elaboration of the pro-coagulant protein, tissue factor. An improved understanding of the pathophysiology of plaque vulnerability and subsequent athero-thrombosis should provide novel insights into improved prevention of athero-thrombotic cardiovascular events.     

稳定型心绞痛患者与急性冠状动脉综合征患者动脉粥样硬化斑块血管内超声对比

目的 应用血管内超声,对比稳定型心绞痛和急性冠状动脉综合征患者动脉粥样硬化斑块的特点.方法 对明确诊断为稳定型心绞痛患者(51例,冠状动脉造影显示病变位于63条血管)以及急性冠状动脉综合征患者(32例,冠状动脉造影显示病变位于46条血管)的动脉粥样硬化斑块形态学特点进行比较.结果 两组患者血管内超声发现,软斑块比例、血管重构指数、最小面积处血管外弹力膜面积、最小面积处斑块负荷和斑块破裂急性冠状动脉综合征组高于稳定型心绞痛组(P<0.05);但血栓检出率两组患者差异没有显著性(P>0.05).结论 目前临床工作中,人们只能半定性诊断易损斑块.如检出软斑块且位于重要血管的近端,不论病变的狭窄程度或检查发现任何斑块加正性血管重构和最小管腔面积≤4 mm+,为急性冠状动脉综合征患者易损斑块.需要尽早介入干预.     

动脉粥样硬化易损斑块动物模型的建立

动脉粥样硬化进展、易损斑块破裂导致主要不良心血管事件发生。易损斑块形成机制和干预措施的研究一直备受瞩目。建立与人体斑块相似的进展性斑块是对易损斑块进行研究的基础及热点。目前,研究者已在多种动物体内建立了多种易损斑块模型。本文对目前建立的易损斑块动物模型进行综述与评价,为完善易损斑块模型的建立提供新思路。     

组织蛋白酶L与动脉粥样硬化

组织蛋白酶L是人体内最重要的组织蛋白酶之一,在心血管病中的作用日益凸显.组织蛋白酶L以其强效的降解弹性蛋白及胶原特性在动脉粥样硬化中介导斑块内巨噬细胞的凋亡,从而影响斑块的稳定性.因此,对于组织蛋白酶L的研究将有助于动脉粥样硬化的诊断及预防.文章对组织蛋白酶L在动脉粥样硬化中的研究现状做一综述.     

白细胞介素18和基质金属蛋白酶9在人冠状动脉粥样硬化斑块中的表达

目的 探讨白细胞介素18和基质金属蛋白酶9在不同程度的人冠状动脉病变中的表达情况及意义.方法收集14例尸检的人冠状动脉共48个冠状动脉标本,根据HE染色将标本分为不稳定斑块组、稳定斑块组和正常对照组.用免疫组织化学及逆转录聚合酶链反应检测白细胞介素18和基质金属蛋白酶9蛋白及mRNA在以上不同类型标本中的分布表达.结果 白细胞介素18和基质金属蛋白酶9表达于冠状动脉粥样硬化斑块区,在不稳定斑块中的表达明显高于稳定斑块.并且二者的表达强度呈正相关.结论 白细胞介素18和基质金属蛋白酶9可能参与冠状动脉粥样硬化斑块的发生、发展,与斑块不稳定性密切相关.并且二者协同参与粥样斑块发展.     

细胞间黏附分子1、血管细胞黏附分子1促进兔动脉粥样硬化斑块内血管新生

目的　探讨细胞间黏附分子1（ICAM-1）、血管细胞黏附分子1（VCAM-1）与兔动脉粥样硬化斑块内血管新生的相关性。方法　25只纯种雄性新西兰大白兔给予球囊拉伤及1%胆固醇饲料喂养建立腹主动脉动脉粥样硬化模型,分别于建模后第4、6、8、10、12周末随机选取5只实验兔行安乐死,取腹主动脉组织脱水,包埋制石蜡切片。石蜡切片进行HE染色以及免疫组织化学染色,分析小鼠抗兔巨噬细胞抗体11、ICAM-1、VCAM-1、血小板内皮细胞黏附分子1的表达。结果　从4周到12周,斑块体积逐渐增大,巨噬细胞数量、ICAM-1与VCAM-1的表达量也逐渐增加。通过HE染色与血小板内皮细胞黏附分子1标记,第8周斑块内可见新生血管出现,并且新生血管的数量在第10周与第12周逐渐增多。相关性分析显示ICAM-1与VCAM-1的表达与斑块内的血管新生密切相关。结论　ICAM-1、VCAM-1与斑块内血管新生密切相关,它们促进了动脉粥样硬化斑块的进展和不稳定。     

心脑血管病危险因素与颈动脉粥样硬化的相关性

目的 探讨心脑血管病危险因素与颈动脉粥样硬化的相关性。方法 选择2010年8月～2013年8月健康体检者916例,依据合并危险因素的数量将受试者分为4组,即0个危险因素组（对照组）226例,1个危险因素组239例,2个危险因素组234例,≥3个危险因素组217例。所有受试者均进行颈动脉超声检测及血生化检测。结果 对照组患者斑块发生率为7.52%,1个危险因素组为15.06%,2个危险因素组为23.93%,≥3个危险因素组为45.16%,从对照组到合并≥3个危险因素组斑块发生率显著上升（P<0.01）。4组受试者IMT分别为0.94±0.32 mm、1.12±0.34 mm、1.25±0.33 mm及1.37±0.39 mm,斑块Crouse积分分别为0.24±0.64、0.58±1.21、0.85±1.26及1.32±1.64。从对照组到合并≥3个危险因素组IMT及斑块Crouse积分逐渐增高（P<0.01）。Logistic回归分析显示,1个危险因素组颈动脉粥样硬化斑块发生率为对照组的1.27倍,2个危险因素组为2.31倍,≥3个危险因素组为4.68倍（P<0.01）。结论 危险因素之间对缺血性脑血管病高危人群颈动脉粥样硬化及斑块的发生具有显著的联合协同作用。     

DAMP-PRR-巨噬细胞途径与动脉粥样硬化斑块的易损性

动脉粥样硬化（As）是一种慢性炎症性疾病,并与自身免疫相关。易损斑块是大多数急性心血管事件的元凶。巨噬细胞对As斑块的易损性起关键作用。本文重点论述巨噬细胞通过“DAMP-PRR”途径如何影响As斑块的易损性,探讨新的抗As治疗策略。     

Toll样受体与动脉粥样硬化易损斑块的关系

Toll样受体作为先天免疫系统中一类病原体相关分子模式识别受体,不仅在动脉粥样硬化发生发展过程中发挥着极为重要的作用,在动脉粥样硬化易损斑块形成中起关键作用。本综述将从四个方面来讨论近年有关Toll样受体与动脉粥样硬化易损斑块关系研究进展。     

Regions of low endothelial shear stress are the sites where coronary plaque progresses and vascular remodelling occurs in humans: an in vivo serial study

Aim We performed serial intracoronary studies of patients withstable coronary artery disease (CAD) to investigate the relationshipsamong baseline endothelial shear stress (ESS), CAD progression,and vascular remodelling. Local haemodynamic factors are criticaldeterminants of plaque progression, vascular remodelling, andclinical CAD manifestations. Methods and results The 3-D anatomy of coronary arteries withlumen obstruction <50% was determined by fusing intracoronaryultrasound and angiographic images in 13 patients at baselineand 8 ± 2 months later. Cross-sectional area of plaque,lumen, and external elastic membrane (EEM), and coronary flowwere measured. Local ESS was calculated. Subsegments with similarESS were categorized based on low (<12 dynes/cm²) and moderate/higherESS (12 dynes/cm²). There were 47 subsegments of similar baselineESS: nine with low ESS and 38 with moderate/higher ESS. Mediansubsegment length was 6.9 mm (25th–75th percentiles =4.2–12.0), and median area of similar ESS of 52.6 mm²(25th–75th percentiles = 26.9–88.0). Subsegmentswith low ESS exhibited plaque progression when compared withsubsegments with moderate/higher ESS (33.3% vs. 7.9%, respectively,P = 0.009 adjusted for clustering of lesions within patients)and constrictive remodelling (44.0% vs. 5.3%, respectively,P = 0.16 adjusted for clustering of lesions within patients).Expansive remodelling occurred with similar frequency in subsegmentswith low vs. moderate/higher baseline ESS. Conclusion Plaque progresses in subsegments with low ESS, associatedwith either constrictive or expansive remodelling. Differentmechanisms are likely responsible for expansive remodellingin different local vascular environments. Early in vivo identificationof arterial subsegments likely to develop high-risk plaque characteristicsmay allow for selective interventions to avoid adverse cardiacoutcomes.     

自噬与动脉粥样硬化的关系及中药的干预作用

自噬是由溶酶体介导的降解胞质内受损的细胞器或蛋白质的代谢过程。适度的自噬对动脉粥样硬化具有保护作用,过度的自噬却会导致细胞死亡,不利于斑块的稳定性。中药能通过多途径、多靶点整合起效防治动脉粥样硬化,其机制很可能与调控动脉粥样硬化相关细胞自噬有关。本文就自噬在动脉粥样硬化中的双重作用、调控自噬对干预动脉粥样硬化的意义、中药对自噬的影响及其在动脉粥样硬化防治中的潜在意义作一综述。     

颈动脉硬化与冠心病的相关性

目的探讨颈动脉内膜中膜厚度(IMT)和颈动脉硬化斑块与冠心病发生的一致性,为临床早期诊治冠心病提供方法和依据。方法将拟诊为冠心病的179例患者行冠状动脉造影检查及颈动脉超声测量颈动脉IMT,并计算斑块积分。根据造影结果将其分为冠心病组和非冠心病组,并分析颈动脉IMT和颈动脉硬化斑块与冠心病发生的关系。结果冠心病组114例,非冠心病组65例,两组颈动脉IMT分别为1.08±0.48 mm、0.85±0.20mm,斑块积分分别为1.61±1.02、1.07±0.43,颈动脉斑块的发生率分别为79.83%(91/114)、21.54%(14/65),差异均有统计学意义(P0.01)。结论颈动脉IMT或颈动脉硬化斑块形成与冠心病的发生具有高度一致性,超声检测颈动脉硬化程度可作为冠心病的筛选参考。     

血管内皮生长因子165对实验性兔动脉粥样硬化斑块形成的影响

目的观察血管内皮生长因子165对动脉粥样硬化斑块形成与发展的影响。方法利用高胆固醇饲料复制动脉粥样硬化兔模型。15只兔随机分为正常对照组、高胆固醇组和血管内皮生长因子组。42天时处死动物,截取胸主动脉进行计量组织学及免疫组织化学分析。结果正常对照组、高胆固醇组和血管内皮生长因子组的斑块面积(0%比1.81%±0.61%比24.12%±3.58%)、斑块周径(0比6.05%±1.62%比25.71%±1.97%)以及斑块最大厚度(0比0.06mm±0.002mm比0.16mm±0.007mm)均存在显著差异(P<0.05)。3组CD34阳性细胞数(cellsmm2)分别为0、12.35±2.02和61.15±7.55(P<0.05)。电镜显示新生血管与动脉粥样斑块相邻,新生血管腔内可见淋巴细胞。血管内皮生长因子组CD34阳性细胞数与斑块面积之间呈正相关(r=0.989,P<0.001)。结论血管内皮生长因子165能促进兔动脉粥样硬化斑块的形成与发展。     

Radial artery intima-media ratio predicts presence of coronary thin-cap fibroatheroma: A frequency domain-optical coherence tomography study

Background

Peripheral arterial disease is a risk factor for cardiac mortality but pathophysiologic mechanisms linking atherosclerosis of peripheral arteries with coronary events in the single patient have not been established.

Method and results

We evaluated by frequency-domain optical coherence tomography (FD-OCT) the possible association between culprit coronary plaque characteristics and proximal radial artery features in a cohort of 51 patients symptomatic coronary artery disease undergoing coronary procedures by transradial route. FD-OCT coronary artery analysis included assessment of TCFA and thrombus. FD-OCT radial artery analysis included intimal thickness index (ITI: intimal area/medial area), intima-media ratio (IMR: the maximum intimal thickness/medial thickness), and percentage of luminal narrowing [%LN: (intimal area + medial area) / external elastic membrane area × 100]. Coronary TCFA and thrombus were detected in 19 (37%) and 7 (14%) patients, respectively. TCFA was significantly associated with higher values of radial artery ITI (0.35 vs. 0.26, p = 0.02) and IMR (0.45 vs. 0.32, p = 0.03), but not with %LN. In contrast, coronary thrombus was only associated with higher %LN (26.7 vs. 22.8, p = 0.02). Multivariate logistic regression analysis identified proximal radial artery IMR (OR 16.3, 95% CI 1.1 to 245.1) as an independent predictor of TCFA.

Conclusions

In patients with symptomatic coronary atherosclerosis, vessel wall modifications at the level of the proximal radial artery are associated with adverse coronary features like TCFA and thrombus.     

高敏C反应蛋白与颈动脉粥样硬化的关系

目的 探讨高敏C反应蛋白和颈动脉粥样硬化的关系.方法 选取在神经内科住院的患者225例(其中脑梗塞患者133例),排除了应激、炎症、自身免疫性疾病等影响高敏C反应蛋白水平的疾病,全部患者行颈部血管彩超检测,观察颈动脉内膜-中膜厚度、斑块的检出情况及斑块评分、管腔的狭窄率,作为评价颈动脉粥样硬化的指标.根据血管彩超的检查结果分为颈动脉粥样硬化组和对照组.用微粒子透射增强免疫法(超敏)检测血浆高敏C反应蛋白的水平.分别比较颈动脉粥样硬化组与对照组高敏C反应蛋白水平的差别,分析高敏C反应蛋白和颈动脉内膜-中膜厚度、斑块评分之间的关系.结果 颈动脉粥样硬化组(130例)与对照组(95例)比较,二者之间的高敏C反应蛋白存在明显差异(P<0.05);偏相关分析显示,高敏C反应蛋白与颈动脉内膜-中膜厚度及斑块评分成正相关,相关系数分别为0.4807和0.3024.结论 颈动脉粥样硬化组较对照组高敏C反应蛋白水平高,高敏C反应蛋白与颈动脉粥样硬化的严重程度成正相关.