CD34在人冠状动脉粥样硬化病变中的表达

目的 探讨CD34在人冠状动脉粥样硬化病变中的表达及其与冠状动脉粥样硬化病变类型、管腔狭窄之间的关系及其意义.方法 选用53例尸检病例的312块冠状动脉组织标本.光镜下诊断冠状动脉粥样硬化病变及其类型,用免疫组织化学计数冠状动脉粥样硬化病变中CD34-阳性内皮细胞微血管和CD68-阳性巨噬细胞.结果 冠状动脉粥样硬化病变内膜CD34-阳性微血管随着冠状动脉粥样硬化病变进展和管腔狭窄程度的加重而增多,分别呈正相关(r=0.344, r=0.285, P<0.01),CD34-阳性微血管在早期和进展期病变之间差异有显著性(P<0.05);冠状动脉粥样硬化病变内膜CD34-阳性微血管在正常胆固醇和高胆固醇组之间差异有显著性(P<0.01);冠状动脉粥样硬化病变内膜CD68-阳性巨噬细胞主要分布在CD34-阳性微血管周围,CD34-阳性微血管和浸润的CD68-阳性巨噬细胞之间呈正相关(r=0.303, P<0.01).结论 人冠状动脉粥样硬化病变内膜CD34-阳性微血管随着冠状动脉粥样硬化病变进展和管腔狭窄程度的加重而增多,CD68-阳性巨噬细胞浸润和高胆固醇血症促进粥样斑块内血管发生.     

CD68与α-平滑肌肌动蛋白在老年冠状动脉粥样硬化病变中的表达及意义

目的:探讨CD68、α-平滑肌肌动蛋白(α-SMA)在老年人冠状动脉粥样硬化(AS)病变和弥漫性内膜增厚(DIT)中的表达,及其与AS病变类型、管腔狭窄之间的关系。方法:选用53例尸检病例的312份冠状动脉组织标本,光镜下诊断DIT和AS病变及其类型,用免疫组织化学和Scion图像软件系统,检测和计算AS病变中CD68-阳性巨噬细胞数和α-SMA阳性面积(%)、冠状动脉管腔狭窄程度、脂质坏死核心面积(%)和钙化基质面积(%)。结果:①CD68阳性巨噬细胞随着病变进展和管腔狭窄程度的加重而增多,呈正相关(r=0.351、0.197,P<0.01),而α-SMA阳性面积随着病变进展和管腔狭窄程度的加重而减少,呈负相关(r=-0.494、-0.362,P<0.01),两者在AS早期和进展期均差异有统计学意义(均P<0.05);②CD68阳性巨噬细胞、α-SMA阳性面积在AS不同病变类型、管腔狭窄程度以及胆固醇分组之间均差异有统计学意义(均P<0.05)。结论:老年人冠状AS病变内膜CD68阳性巨噬细胞增多及α-SMA阳性面积减少自始至终促进病变进展。     

冠状动脉粥样硬化病变类型与α-平滑肌肌动蛋白含量的关系

目的:探讨人类冠状动脉粥样硬化病变类型与内膜α-平滑肌肌动蛋白(α-SMA)含量的关系.方法:选用53例尸检病例的312块冠状动脉组织.经苏木精-伊红染色诊断冠状动脉粥样硬化病变及其类型,用免疫组化和Scion图像软件系统,测定和计算冠状动脉标本中α-SMA阳性面积%.结果:在冠状动脉粥样病变类型中, 5% (16/312)为Ⅰ型,10% (31/312) 为Ⅱ型,21% (66/312) 为Ⅲ型, 4% (14/312)为Ⅳ型, 18% (55/312) 为Ⅴ型和2% (6/312)为Ⅵ型.冠状动脉粥样硬化病变内膜α-SMA阳性面积%随着病变进展和管腔狭窄程度的加重而减少,分别呈负相关 (r=-0.494,P<0.01,r=-0.362,P<0.01).结论:人类冠状动脉粥样硬化病变内膜α-SMA阳性面积%随着冠状动脉粥样硬化病变程度的加重而减少.     

非高密度脂蛋白胆固醇对冠状动脉病变的影响

目的 通过回顾性研究探讨不同血脂指标的控制对冠状动脉粥样硬化病变加重的影响.方法 入选在我院成功行支架植入术并于3个月后至1年内回院复查冠状动脉造影的患者,复查时间平均为7.4 ±2.2个月.未行介入治疗的其它冠状动脉若发生狭窄加重大于原来的25%以上定为粥样硬化病变加重.发生冠状动脉粥样硬化病变加重者95例,无变化者307例.患者于入院即介入手术前及复查冠状动脉造影前均测定了血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇,非高密度脂蛋白胆固醇应用公式(总胆固醇-高密度脂蛋白胆固醇)计算.结果 复查时病变加重组和无变化组总胆固醇(4.62±1.14 mmol/L比4.26±1.01 mmol/L)、低密度脂蛋白胆固醇(2.51±0.93 mmol/L比2.25±0.75 mmol/L)及非高密度脂蛋白胆固醇水平(3.52±1.12mmoL/L比3.20±0.98 mmol/L),三者差异均有显著性(P<0.05),应用Logistic多因素分析显示均与病变加重发生 相关.结论 总胆固醇、低密度脂蛋白胆目醇及非高密度脂蛋白胆固醇水平是未行介入治疗的其它冠状动脉粥样硬化病变加重的重要危险因素,应重视冠心病患者非高密度脂蛋白胆固醇水平的有效控制.     

冠状动脉狭窄短期加重1例报道

正冠心病主要是由于冠状动脉粥样硬化导致管腔狭窄、甚至闭塞,引起心肌缺血缺氧,甚至坏死的疾病。随着人们生活水平的提高和生活方式的改变,冠心病已逐渐成为人类的头号杀手。而冠状动脉粥样硬化是在各种危险因素及炎症因子作用下,在冠状动脉内形成粥样斑块,主要由脂质核心和表面的纤维帽构成,其形成和发展是一个比较缓慢的过程。故临床上冠状动脉狭窄的进展也比较缓慢,但近期我们在临床上发现1例冠状动脉病变进展迅速的患者,现将该     

急性心肌梗塞与冠状动脉病变

急性心肌梗塞(AMI)绝大多数与冠状动脉(冠脉)粥样硬化病变有关。由于冠脉痉挛、斑块出血及/或破溃、血栓形成等冠脉急性病变参与了AMI发病,因此AMI与粥样硬化病变所累及的冠脉范围以及造成管腔狭窄程度之间常无恒定的关系。AMI发     

动脉粥样硬化与冠状动脉血流的关系

人类冠状动脉粥样硬化主要发生在较大冠状动脉近端6～8厘米处,常呈现为由各种脂质(包括胆固醇和胆固醇酯)、细胞以及由细胞合成之纤维蛋白所组成的血管内膜斑块。成熟斑块其占据空间的二个主要成份是纤维盖和坏死的粥样核心,这些成份合在一起可致使管腔发生重度狭窄。形成人类斑块(包括纤维盖)的主要细胞是平滑肌细胞,后者推测是从血管中层移行来的,并伴有血管内膜中这些细胞的过度增殖(有丝分裂)。脂质-胆固醇混合物似乎主     

多排螺旋CT对冠状动脉斑块特征评价的精确性与血管内超声的比较

目的:对比血管内超声(IVUS),评价多排螺旋CT(MSCT)判断冠状动脉粥样硬化斑块特征的精确性.方法:连续性入选2007-08-2008-12期间在解放军总医院心内科诊断为冠心病并行MSCT、IVUS检查者,分别利用IVUS、MSCT方法测量同一病变的同一截面的血管截面积(V-CSA)、管腔截面积(L-CSA)、狭窄程度、斑块负荷(BP)、重构指数(RI)等指标;对比IVUS,计算MSCT判断狭窄程度及斑块性质的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV).结果:与IVUS对比,MSCT显示冠状动脉粥样硬化斑块的敏感性为98.0%,特异性为90.1%,PPV为93.0%,NPV为97.0%;显示狭窄程度＞50.0%病变的敏感性为96.5%,特异性为97.1%,PPV为98.2%,NPV为94.3%;MSCT与IVUS测量冠状动脉同一病变同一截面下的V-CSA、L-CSA、BP及RI,各指标之间存在明显直线相关关系;MSCT判断脂质斑块的敏感性为88.9%,特异性为84.9%;纤维斑块的敏感性为73.3%,特异性为91.2%;钙化斑块的敏感性为95.7%,特异性为100%.结论:MSCT在诊断冠心病、判断冠状动脉粥样硬化斑块特征方面有较好的精确性,可做为无创性评估易损斑块的手段.     

原发性高血压左室肥厚患者冠状动脉粥样硬化狭窄特点

目的:探讨原发性高血压(EH)伴左室肥厚(LVH)患者冠状动脉粥样硬化狭窄特点。方法:选择经过冠状动脉造影的EH患者566例,伴LVH者140例(LVH组),与单纯EH患者426例(对照组)对比分析冠状动脉粥样硬化狭窄的部位、狭窄的程度、狭窄的范围等的差异。结果:LVH组与对照组比较,LVH组患者发生冠状动脉粥样硬化狭窄的概率明显升高(P<0.01),其危险性增加5.09倍。同时,LVH组发生左前降支冠状动脉粥样硬化狭窄概率显著高于对照组(P<0.01),在其他部位冠状动脉粥样硬化狭窄程度2组比较差异无统计学意义(P>0.05)。LVH组冠状动脉狭窄患者运动平板试验的心肌缺血检出率为33.1%(42/127),而对照组冠状动脉狭窄患者的心肌缺血检出率为12.5%(35/280),P<0.05。在传统冠状动脉粥样硬化危险因素中,只有血压与LVH存在协同效应(P<0.05)。结论:EH伴LVH患者冠状动脉粥样硬化狭窄发生率显著升高,左前降支是主要狭窄部位,而且更易于发生心肌缺血。     

症状性颈动脉系统动脉硬化斑块颅内外分布的相关性研究

目的探讨症状性颈动脉系统粥样硬化斑块颅内、外分布的相关性。方法选取有脑梗死或短暂性脑缺血发作患者55例,其中脑梗死27例(49.1%),短暂性脑缺血发作28例(50.9%),同时进行颅内、外颈动脉MRI,分析两者之间的相关性。结果颅外颈动脉:最大管壁厚度、粥样硬化斑块累及范围及管腔狭窄程度分别为(3.7±1.6)mm、(27.7±15.0)mm及(37.9±30.6)%;37例(67.3%)斑块内伴有钙化,24例(43.6%)斑块内伴有出血,25例(45.5%)斑块内伴有富脂质坏死核,13例(23.6%)斑块表面纤维帽破裂;颅内颈动脉:大脑中动脉及前循环(包括大脑前、中动脉)的管腔狭窄度分别为(37.2±26.5)%和(37.5±26.2)%。大脑中动脉狭窄与颅外颈动脉狭窄及最大管壁厚度有相关性(r=0.866,r=0.564,P<0.01)。前循环狭窄与颅外颈动脉狭窄及最大管壁厚度有相关性(r=0.879,r=0.598,P<0.01)。结论颅内、外颈动脉粥样硬化性疾病的严重性之间有显著的相关性。颅外颈动脉粥样硬化性斑块可以作为预测颅内颈动脉粥样硬化性疾病的严重程度指标。     

Niemann-Pick C heterozygosity confers resistance to lesional necrosis and macrophage apoptosis in murine atherosclerosis

Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis and likely promotes plaque instability, a precursor of acute vascular events. Macrophages in advanced lesions accumulate large amounts of unesterified cholesterol, which is a potent inducer of macrophage apoptosis. We have shown recently that induction of apoptosis in cultured macrophages requires cholesterol trafficking to the endoplasmic reticulum (ER). Moreover, macrophages from mice with a heterozygous mutation in the cholesterol-trafficking protein Npc1 have a selective defect in cholesterol trafficking to the ER and are protected from cholesterol-induced apoptosis. The goal of the present study was to test the importance of intracellular cholesterol trafficking in atherosclerotic lesional macrophage death by comparing lesion morphology in Npc1+/+;Apoe-/- and Npc1+/-;Apoe-/- mice. Although advanced lesions in Npc1+/+;Apoe-/- mice had extensive acellular areas that were rich in unesterified cholesterol and macrophage debris, the lesions of Npc1+/-;Apoe-/- mice were substantially more cellular and less necrotic. Moreover, compared with Npc1+/-;Apoe-/- lesions, Npc1+/+;Apoe-/- lesions had a greater number of large, TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling)-positive areas surrounding necrotic areas, indicative of macrophage apoptosis. These differences were observed despite similar total lesion area and similar plasma lipid levels in the two groups of mice. These data provide in vivo evidence that intact intracellular cholesterol trafficking is important for macrophage apoptosis in advanced atherosclerotic lesions and that the ER-based model of cholesterol-induced cytotoxicity is physiologically relevant. Moreover, by showing that lesional necrosis can be diminished by a subtle defect in intracellular trafficking, these findings suggest therapeutic strategies to stabilize atherosclerotic plaques.     

Association between complex coronary artery stenosis and unstable angina and the extent of plaque inflammation

PURPOSE: Patients with unstable coronary syndromes often have complex morphology of coronary stenoses at angiography. We evaluated the association between qualitative assessment of coronary stenoses and plaque inflammation determined by immunohistochemistry. METHODS: A total of 79 patients with unstable (n = 46) or stable angina (n = 33) underwent directional coronary atherectomy for culprit lesions. Qualitative analysis of coronary angiograms was performed using a modified Ambrose classification. Coronary lesions were categorized as either simple (concentric and eccentric type I, n = 29) or complex (eccentric type II and multiple irregularities, n = 50). Cryostat sections of retrieved atherosclerotic specimens were stained immunohistochemically with monoclonal antibodies, alpha-actin (smooth muscle cells), CD68 (macrophages), and CD3 (T lymphocytes). The extent of atherosclerotic inflammation within each coronary lesion was determined by the percentage of immunopositive macrophages per total tissue area (including smooth muscle cells) and the number of T lymphocytes per mm(2). RESULTS: The mean (+/- SD) percentage of macrophages in atherectomy specimens from patients with unstable angina was greater than in specimens from patients with stable angina (21% +/- 14% vs. 13% +/- 10%, P = 0.01); similar results were seen when complex coronary lesions were compared with simple lesions (23% +/- 13% vs. 9% +/- 8%, P <0.001). In multivariate linear regression models, the combination of unstable angina and lesion complexity was strongly associated with the percentage of plaque macrophages. CONCLUSION: The extent of atherosclerotic plaque inflammation is associated with angiographic grading of coronary lesion complexity and unstable angina.     

Cathepsin L is significantly associated with apoptosis and plaque destabilization in human atherosclerosis

ObjectiveHuman atherosclerotic lesions overexpress elastolytic and collagenolytic cathepsins with unclear pathological implications. The aim of this study was to investigate the relationship among expression of cathepsin L, macrophage apoptosis in coronary artery disease (CAD) patients, clinical symptoms and plaque severity of human carotid atheroma.Methods and resultsQuantitative immunohistochemical analysis of human carotid atherosclerotic lesions (n = 49) showed that expression of lysosomal cathepsin L was significantly increased in atherosclerotic plaques with formation of the necrotic core and rupture of the cap. In those plaques, cathepsin L was associated mainly with CD68-positive macrophages, whereas significant lower levels of smooth muscle cell actin were detected. The expression of cathepsin L in these plaques was also correlated with apoptosis and the stress protein ferritin. Plaques from symptomatic patients showed greater increased levels of cathepsin L than those from asymptomatic patients. Human monocyte-derived macrophages from CAD patients (n = 7) showed significantly higher levels of cathepsin L, cellular lipids and apoptosis versus cells from matched healthy donors (n = 7). 7Beta-hydroxycholesterol significantly enhanced cathepsin L in cells from healthy donors but not in cells from CAD patients. Moreover, macrophage apoptosis was significantly correlated with expression of cathepsin L in cell nuclei and membranes.ConclusionThe results suggest that cathepsin L is involved in death of macrophages, necrotic core formation and development of atherosclerotic plaque instability. Macrophage lysosomal cathepsin L and related apoptosis may be potential targets for modulation or imaging of vulnerable plaques in human atherosclerosis.     

Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

Value of the spectral analysis of radiofrequency intravascular ultrasound data in the evaluation of nonsignificant coronary lesions in chronic CHD patients

Plaque complication depends on its composition and phenotype rather than on the degree of stenosis. Plaque rupture predominantly occurs in areas with large lipid core rich in cholesterol and thin fibrous cap. Features of unstable atheromas are mostly described in patients with acute coronary syndromes (ACS). The aim of our study was to assess the plaque characterization and arterial remodeling process in non-significant stenoses of patients with chronic coronary heart disease (CHD) using intravascular ultrasound (IVUS) radiofrequency (RF) data. Methods. The study included 22 stable patients (68% men, mean age 54+/-6 years) with CHD and clinical indications for coronary angiography (CAG). Diameter stenosis of the target coronary artery for IVUS procedure had to be less than 60%. Thin-cap fibroatheroma (TCFA) was defined as plaque burden >40% and amount of NC >10% without detectable overlying fibrous cap segment. Results. Sample size calculations based on the IVUS evaluation showed 54 atheromas in 29 target arteries. Features of vulnerability determined as TCFA were detected in 14 (26%) lesions. Compared with stable lesions VPs were associated with a greater plaque burden (48.5+/-8.0 mm2 vs 55.8+/-9.3 mm2, p=0.03), larger quantity of necrotic core (37.1+/-9.1% vs 24.0+/-12.6%, p=0.0045) and calcium content (22.7+/-8.5% vs 5.6+/-5.2%, p<0.000l), and less fibrous component (34.8+/-7.0% vs 60.4+/-12.4%, p<0.0001), respectively. Significant correlation was obtained between positive remodeling (defined as remodeling index >1.05) and NC percent area (r=0.389. p=0.005). Conclusion. In chronic CHD patients about 25% of atherosclerotic lesions responsible for less than 60% stenosis could be classified as vulnerable plaques. These borderline lesions contain more necrotic and calcium components compared with stable plaques, and are associated with positive arterial remodeling.     

Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage

Observational studies of necrotic core progression identify intraplaque hemorrhage as a critical factor in atherosclerotic plaque growth and destabilization. The rapid accumulation of erythrocyte membranes causes an abrupt change in plaque substrate characterized by increased free cholesterol within the lipid core and excessive macrophage infiltration. Neoangiogenesis is associated closely with plaque progression, and microvascular incompetence is a likely source of intraplaque hemorrhage. Intimal neovascularization is predominantly thought to arise from the adventitia, where there are a plethora of pre-existing vasa vasorum. In lesions that have early necrotic cores, the majority of vessels invading from the adventitia occur at specific sites of medial wall disruption. A breech in the medial wall likely facilitates the rapid in-growth of microvessels from the adventitia, and exposure to an atherosclerotic environment stimulates abnormal vascular development characterized by disorganized branching and immature endothelial tubes with "leaky" imperfect linings. This network of immature blood vessels is a viable source of intraplaque hemorrhage providing erythrocyte-derived phospholipids and free cholesterol. The rapid change in plaque substrate caused by the excessive accumulation of erythrocytes may promote the transition from a stable to an unstable lesion. This review discusses the potential role of intraplaque vasa vasorum in lesion instability as it relates to plaque rupture.     

Regression of an atherosclerotic coronary artery plaque demonstrated by multislice spiral computed tomography in a patient with stable angina pectoris

Multislice spiral computed tomography (MSCT) permits direct visualization of not only coronary artery stenosis but also atherosclerotic plaques in patients with coronary artery disease. In this report, we describe a patient with stable angina in whom the regression of the plaque was documented by serial MSCT examinations. In the patient, a 46-year-old man with stable angina, MSCT revealed a stenotic lesion at the proximal portion of the left anterior descending artery. Axial, curved multiplanar reconstruction and cross-sectional images consistently depicted a protruding computed tomography low-signal mass suggesting an atherosclerotic plaque. Intracoronary ultrasound (ICUS) also documented an eccentric soft plaque with an echo-lucent mass suggesting a lipid core. Lipid-lowering therapy with pravastatin was started. Follow-up MSCT performed 7 months later documented an increase in the luminal area while the external vessel area remained unchanged. The regression of the plaque was also confirmed by a follow-up ICUS study. MSCT was thought to be feasible for serial evaluation of the plaque size and texture.     

Shrinkage of human coronary arteries is an important determinant of de novo atherosclerotic luminal stenosis: an in vivo intravascular ultrasound study

Objective—To assess the occurrence of arterial remodelling types and its relation with the severity of luminal stenosis in atherosclerotic coronary arteries.
Patients and methods—Twenty one de novo coronary lesions of 20 patients, who were scheduled for percutaneous transluminal coronary angioplasty (PTCA), were investigated with intravascular ultrasound before PTCA. Local arterial remodelling at the lesion site was studied by measuring the cross sectional area circumscribed by the external elastic lamina (EEL) relative to the reference site: (EEL area lesion/reference EEL area) × 100%. Three groups were defined. Group A: relative EEL area of less than 95% (shrinkage), group B: relative EEL area between 95% and 105% (no remodelling), group C: relative increase in EEL area of more than 105% (compensatory enlargement).
Results—All three types of remodelling were observed at the lesion site: group A (shrinkage) n = 8, group B (no remodelling) n = 5, group C (compensatory enlargement) n = 8. The mean (SD) relative EEL area at the lesion site in group A and C was 83(9)% and 132(30)%, respectively. In group A, 33% of the luminal area stenosis at the lesion site was caused by shrinkage of the artery. In contrast, group C showed that 87% of the plaque area did not contribute to luminal area stenosis because of compensatory arterial enlargement.
Conclusions—These results show that both compensatory enlargement and paradoxical shrinkage occurs in the atherosclerotic coronary artery. Next to plaque accumulation, the type of atherosclerotic remodelling is an important determinant of luminal narrowing.

Keywords: coronary arteries; atherosclerosis; remodelling; intravascular ultrasound     

Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques

ObjectiveThe Factor Seven Activating Protease (FSAP) is known to influence fibrinolysis and to play a critical role in the inhibition of vascular smooth muscle cell (VSMC) proliferation and migration as well as neointima formation. In order to define the role of FSAP in vascular pathophysiology we have investigated the expression of FSAP protein and mRNA in human vascular cells and coronary atherosclerotic plaques with defined clinical features.Methods and resultsDirectional coronary atherectomy (DCA) specimens from 40 lesions were analyzed for FSAP antigen and mRNA expression. Higher level of FSAP mRNA (p < 0.001) as well as FSAP immunostaining (p < 0.005) was observed in patients with acute coronary syndromes compared to patients with stable angina pectoris. FSAP antigen was found to be focally accumulated in hypocellular and lipid-rich areas within the necrotic core of atherosclerotic plaques. FSAP was also co-localized with CD11b/CD68 expressing cells in macrophage-rich shoulder regions of the plaques. Monocyte-derived macrophages expressed FSAP in vitro and this was further induced by pro-inflammatory mediators.ConclusionsFSAP accumulation in coronary atherosclerotic lesions is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. The higher expression of FSAP in unstable plaques suggests that it may destabilise plaque through reducing VSMC proliferation/migration and altering the hemostatic balance.