Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic arteries of apolipoprotein E knockout mice

The brachiocephalic arteries of fat-fed apolipoprotein E knockout mice develop plaques that frequently rupture and form luminal thromboses. The morphological characteristics of plaques without evidence of instability or with healed previous ruptures (intact) and vessels with acutely ruptured plaques (ruptured) have now been defined, to understand the process of plaque destabilization in more detail. Ninety-eight apolipoprotein E knockout mice were fed a diet supplemented with 21% lard and 0.15% cholesterol, for 5 to 59 weeks. Of these 98 mice, 51 had an acutely ruptured plaque in the brachiocephalic artery. Ruptured and intact plaques differed in terms of plaque cross-sectional area (intact, 0.109+/-0.016 mm2; ruptured, 0.192+/-0.009 mm2; P=0.0005), luminal occlusion (intact, 35.3+/-3.3%; ruptured, 57.7+/-1.9%; P<0.0001), the number of buried caps within the lesion (intact, 1.06+/-0.12; ruptured, 2.66+/-0.16; P<0.0001), fibrous cap thickness (intact, 4.7+/-0.6 microm; ruptured, 2.0+/-0.3 microm; P=0.0004), and lipid fractional volume (intact, 35.9+/-3.0%; ruptured, 50.7+/-2.2%; P=0.0019). This study confirms that plaque rupture is a frequent occurrence in the brachiocephalic arteries of apolipoprotein E knockout mice on a high-fat diet. The data also show that ruptured plaques in these mice show many of the characteristics of vulnerable plaques in humans. This supports the use of this model in studies of the mechanisms and therapy of plaque rupture.     

液氮冻伤术建立动脉粥样硬化斑块兔模型

目的创建一种操作简单、经济实用的动脉粥样硬化斑块动物模型。方法 15只健康纯种雄性新西兰白兔实施右颈总动脉内膜液氮冻伤术,结合高脂饲料喂养,术后8周处死动物,取出双侧颈总动脉对比,经病理形态学、免疫组织化学和生化检测观察动脉粥样硬化斑块形成情况。结果 8周后,所有兔右颈总动脉均可见大量动脉粥样硬化斑块形成,而左颈总动脉均无斑块形成;兔血清中脂质水平明显升高(P<0.01);所建立的斑块在组织结构、细胞构成、生长特征和脂质沉积方面与人类斑块相似。结论液氮冻伤术能快速建立典型的动脉粥样硬化斑块模型,从而为研究动脉粥样硬化相关的心脑血管疾病提供一个简便、高效的新型动物模型。     

Animal models of spontaneous plaque rupture: The holy grail of experimental atherosclerosis research

Throughout the history of atherosclerosis research we have sought animal models of the disease process that exhibit high frequencies of the features that make human plaque a clinical risk: plaque rupture, mural thrombosis, and intra-plaque hemorrhage. This type of model is needed to determine the mechanisms by which plaques rupture and to design and test therapeutic interventions for stabilizing plaques. Studies of domestic and exotic animals have shown that most species will spontaneously develop fatty streaks and in some cases atheromatous lesions with sufficient time, but that rupture and thrombosis is exceedingly rare. Even with addition of fat and cholesterol to the diet, lesion development is accelerated but does not increase the frequency with which plaques rupture in most animal models. However, recently we have observed high frequencies of intra-plaque hemorrhage in the innominate/brachiocephalic arteries of older, chow-fed, hyperlipidemic, apolipoprotein E-deficient mice, and high frequencies of plaque rupture with mural thrombus in younger apolipoprotein E-deficient mice fed a high-fat diet. This suggests that plaque rupture and secondary thrombosis are frequent and reproducible occurrences at specific sites in apolipoprotein E-deficient mice, and that the timing and pathobiology of the ruptures are influenced by lipid status in this murine model.     

Increased vulnerability of pre-existing atherosclerosis in ApoE-deficient mice following adenovirus-mediated Fas ligand gene transfer

OBJECTIVE: The death receptor Fas and Fas ligand (FasL) are present in human advanced atherosclerotic plaques. The activation of the Fas/FasL pathway of apoptosis has been implicated in plaque vulnerability. In the present study, we investigated whether overexpression of FasL in pre-existing atherosclerotic lesions can induce lesion remodelling and rupture-related events. METHODS AND RESULTS: Carotid atherogenesis was initiated in apolipoprotein E-deficient mice by placement of a perivascular silastic collar. The resulting plaques were incubated transluminally with recombinant adenovirus carrying FasL (Ad-FasL, lateral) or control beta-galactosidase (Ad-LacZ, contralateral). Transfection was restricted to the smooth muscle cell-rich cap of the plaque, and FasL expression led to a three-fold increase in apoptosis in the cap one day after gene transfer. Three days after gene transfer, FasL expression led to a 38% reduction in the number of cap cells. Two weeks after Ad-FasL transfer, non-thrombotic rupture, intra-plaque haemorrhage, buried caps and iron deposits were observed in 6 out of 17 Ad-FasL-treated carotid arteries versus 0 out of 17 controls (P=0.009), indicative of enhanced plaque vulnerability. CONCLUSIONS: These data demonstrate that advanced murine plaques are sensitive to Fas/FasL-induced apoptosis, which may indicate that stimulation of this pathway could result in plaque remodelling towards a more vulnerable phenotype.     

Assessment of unstable atherosclerosis in mice

There is an urgent need for representative animal models where prospective examination of the events leading up to plaque rupture and the rupture process itself can be performed. Recently, reports have begun to emerge that apolipoprotein E and low density lipoprotein receptor knockout mice may spontaneously develop unstable atherosclerosis, with plaques in certain parts of the arterial tree showing features suggestive of plaque rupture. Here we discuss the problems inherent in applying definitions of plaque rupture as seen in human arteries to mice; the anatomic locations in mice where unstable plaques do and do not occur; methods of inducing plaque instability in mice; and how to assess plaque stability in mice. These considerations lead us to a number of general recommendations.     

老龄ApoE基因敲除小鼠动脉粥样硬化斑块的病理观察

目的：观察西方饮食喂养的老龄（≥48周）ApoE基因敲除小鼠血管动脉粥样硬化斑块的病理组织学状况。方法：选取6周龄雄性纯合子ApoE基因敲除小鼠30只，均予以西方饮食喂养，分别在喂养42周（48周龄）、54周（60周龄）、66周（72周龄）时，随机各取10只，取无名动脉做病理检测。酶法检测血脂情况，冰冻切片光镜下观察无名动脉粥样硬化斑块病理情况，图像分析管腔及斑块面积，免疫组化染色观察斑块中骨桥蛋白、α肌动蛋白的表达。von Kossa染色观察斑块钙化情况。结果：西方饮食喂养48周龄后，ApoE基因敲除小鼠主动脉弓内形成广泛而且典型的动脉粥样硬化成熟斑块，60周龄时，无名动脉内斑块面积、其与血管面积比率和自发破裂率最高，不稳定斑块比例最大（P〈0．05～〈0．01）。结论：长期西方饮食喂养ApoE基因敲除小鼠，是研究动脉粥样硬化成熟斑块很好的动物模型。     

Multiple ruptures of atherosclerotic plaques in acute coronary syndrome. Endocoronary ultrasonography study of three arteries

The aim of this study was to assess the three coronary arteries systematically by endocoronary ultrasonography in patients with unstable angina to check the hypothesis of global destabilisation of atherosclerotic plaques in acute coronary syndromes (ACS). Sixty two coronary arteries were examined (2.6 per patient). Fifty plaque ruptures were diagnosed (2.08 per patient). Rupture of a plaque of the culprit lesion of the ACS was clearly detected in 9 patients (37.5%). At least one ruptured plaque on a site other than the culprit lesion was observed in 19 patients (79%), on another artery in 70.8% of cases and on two other arteries in 12.5% of cases. A complete endocoronary ultrasonic examination of the three coronary arteries in patients with a first ACS demonstrated that: multiple atherosclerotic plaque rupture may be detected by endocoronary ultrasonography; these multiple plaque ruptures occur simultaneously with the culprit lesion; they are frequent and can be situated on the three main coronary vessels and multiple plaque rupture other than the culprit lesion are less severe, non stenotic and less calcified. Thus, although a single lesion is clinically symptomatic, ACS seems to be associated with global coronary instability.     

Usefulness of high-frequency vascular ultrasound imaging and serum inflammatory markers to predict plaque rupture in patients with stable and unstable angina pectoris

It remains unclear what kind of morphologic and biochemical features best predict plaque rupture in patients with angina pectoris (AP). This study aimed to investigate whether combined high-frequency vascular ultrasound imaging and measurements of serum inflammatory biomarkers can predict coronary plaque ruptures in patients with AP. The study population consisted of 20 patients with stable AP and 40 patients with unstable AP. High-frequency vascular ultrasound imaging was performed in the 2 groups to measure intima-media thickness, the plaque acoustic density of the common carotid arteries, and the flow-mediated dilation of the brachial arteries. Serum lipid profile and inflammatory biomarkers were measured in all patients. Using intravascular ultrasound, a list of coronary imaging parameters was obtained. A multivariate logistic regression model was applied to calculate the odds ratio of each parameter to predict coronary plaque ruptures detected by intravascular ultrasound. Of 139 coronary artery plaques identified by intravascular ultrasound, 48 plaques (9 in stable AP and 39 in unstable AP) developed ruptures. Among measured parameters, the values of carotid intima-media thickness, coronary external elastic membrane area, plaque area, plaque burden, plaque eccentric index and remodeling index, serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly higher in unstable AP than in stable AP (p <0.05 to 0.01). Of these parameters, carotid intima-media thickness, serum high-sensitivity C-reactive protein, and the coronary remodeling index were found to be significant predictors of coronary plaque rupture, with odds ratios of 9.51 (95% confidence interval 1.29 to 21.81), 3.02 (95% confidence interval 1.01 to 7.65), and 0.01 (95% confidence interval 0.00 to 0.34), respectively. In conclusion, combined high-frequency ultrasound imaging of coronary and carotid arteries and measurements of serum inflammatory markers are able to predict coronary plaque ruptures in patients with AP.     

Micro-ultrasound imaging assessment of carotid plaque characteristics in apolipoprotein-E knockout mice

This study was aimed to test the hypothesis that noninvasive assessment of carotid plaques can be achieved by high-resolution micro-ultrasound imaging in apolipoprotein-E knockout (apoE-KO) mice. Forty-two male apoE-KO mice were fed a high-fat diet and atherosclerotic lesions in the left common carotid artery were induced by perivascular placement of constrictive collars. Eight weeks after surgery, all mice were divided into interventional group (n=21) which received mental stress stimulation and intraperitoneal injection of lipopolysaccharide, and control group (n=21) which received only 0.9% sodium chloride solution for 4 weeks. Plaque morphology and flow velocities were evaluated by micro-ultrasonography. The results showed that micro-ultrasound imaging and corresponding cross-sectional histopathology data revealed positive correlations for plaque area, intima-medial thickness (IMT), eccentric index (EI) and remodeling index (RI) (all p<0.05). Ultrasound-derived IMT, EI and RI in the ruptured plaques were significantly greater than those in the nonruptured plaques (all p<0.05). Maximal flow velocity (Vmax) was higher in the ruptured plaque sites compared with nonruptured plaques sites (p<0.001). Multivariate logistic regression analysis revealed that IMT and Vmax were independent predictors of plaque rupture. In conclusion, micro-ultrasound imaging provides a reliable approach to the noninvasive and quantitative assessment of carotid plaques in apoE-KO mice.     

Role of cathepsin K in structural changes in brachiocephalic artery during progression of atherosclerosis in apoE-deficient mice

Cathepsin K, a potent extracellular matrix degrading cysteine protease, has been linked to the pathogenesis of osteoporosis, arthritis, cardiovascular and respiratory diseases. Here, we report the effects of cathepsin K deficiency (ctsK−/−) on atherosclerotic plaque formation in brachiocephalic arteries in an aggressive atherosclerosis model using apoE-deficient mice on cholate-containing high fat diet (HFD). On this diet, apoE−/− mice displayed severe lesions with buried fibrous caps after 8 weeks, whereas the apoE−/−ctsK−/− mice revealed a significantly decreased number of buried fibrous caps accompanied by increased collagen content in plaque areas and fibrous cap thickness. After 16 weeks of HFD, ctsK−/− mice had smaller plaque areas and maintained the structure of the tunica media in terms of their smooth muscle cell content and elastic lamina integrity. Overall macrophage content in the tunica media was lower in ctsK−/− mice but higher in the plaque area after 8 weeks of HFD. Decreased apoptosis rates in atherosclerotic plaques in brachiocephalic arteries of cathepsin K-deficient indicated a lower level of inflammation. In conclusion, cathepsin K deficiency appears to increase lesion stability in brachiocephalic arteries by maintaining the integrity of the tunica media and by decreasing plaque vulnerability to rupture.     

2型糖尿病患者颈动脉粥样硬化斑块与骨密度的相关性分析

目的探讨住院2型糖尿病(T2DM)患者不同性别骨量减少(包括骨质疏松与低骨量)相关影响因素及其与颈动脉粥样硬化斑块之间的关系。方法回顾性分析720例T2DM患者的临床资料,将入选对象分为男性组和女性组,每组再分为骨量正常组和骨量减少组,颈动脉有斑块组和颈动脉无斑块组。结果在男性骨量减少组(77例)中,存在粥样斑块68例(88.31%),与骨量正常组(164例)比较,骨量减少组粥样斑块的发生率明显升高(P0.05);斑块形成组骨密度(BMD)明显减低(P0.05)。在女性骨量减少组(255例)中,存在粥样斑块191例(74.90%),与骨量正常组(224例)比较,骨量减少组粥样斑块的发生率明显升高(P0.05);斑块形成组骨密度明显减低(P0.05)。二元Logistic回归分析显示,男性骨量减少的影响因素有年龄(OR=1.059,P=0.002),体质指数(BMI)(OR=0.853,P=0.004),空腹血糖(FBG)(OR=1.138,P=0.044),有无颈动脉斑块(OR=2.514,P=0.035)。女性骨量减少的影响因素有年龄(OR=1.117,P=0.000),绝经年龄(OR=0.946,P=0.031),BMI(OR=0.910,P=0.003)。结论 T2DM患者颈动脉粥样硬化斑块与骨量减少密切相关。女性患者由于增龄等共同危险因素的存在,二者常相伴发生,然而在男性患者中,颈动脉粥样硬化斑块的形成是骨质疏松的危险因素,因此,颈动脉硬化的发展常伴有骨量变化,易发生骨质疏松。     

影像学检查对缺血性脑血管病患者颈动脉粥样硬化斑块的研究

目的采用双源CT血管造影(CTA)和高分辨MRI,探讨缺血性脑血管病患者颈总动脉分叉处粥样硬化斑块的性质、成分和动脉管腔狭窄程度与缺血性脑血管病的关系。方法选择缺血性脑血管病患者40例,经颈部CTA检测出颈总动脉分叉处粥样硬化斑块并伴管腔狭窄,再接受MRI扫描;分析颈动脉粥样斑块的性质、成分及管腔狭窄程度。结果 40例患者中,CTA检出斑块61个,其中混合性斑块31个;钙化性斑块18个;软斑块12个。高血压30例,检出斑块49个;无高血压10例,检出斑块12个。MRI检出斑块61个,其中Ⅲ型14个;Ⅳ～Ⅴ型23个,Ⅵ型6个;Ⅶ型18个。斑块内溃疡6例;颈动脉粥样硬化斑块造成同侧急性脑梗死14例,双侧颈动脉斑块造成双侧脑梗死10例,一侧颈动脉检出粥样斑块而对侧发生脑梗死2例。结论缺血性脑血管病患者颈动脉粥样硬化斑块主要以混合性斑块为主,双侧好发;高血压患者斑块发生率高于无高血压患者;颈动脉粥样硬化斑块造成同侧脑梗死发生率较高。     

The role of ultrasonography of the peripheral arteries in diagnosing coronary artery disease

Atherosclerosis develops simultaneously in multiple arterial beds, that creates opportunity to diagnose of coronary artery disease. Aim of the study was the evaluation of association between atherosclerotic involvement of peripheral arteries assessed by ultrasound and significant coronary artery disease revealed by angiography. Study included 410 patients, (73% males), mean age 56.0 +/- 9.5 year scheduled for coronary angiography. During ultrasound examination of common carotid and common femoral arteries arterial wall intima-media (IMT) thickness and atherosclerotic plaques presence were assessed. Significant coronary artery disease (CAD) was diagnosed with coronary angiography as diameter stenosis > 50%. Intimo-media thickness (IMT) of common carotid arteries did not differ between groups with and without significant coronary artery disease (right 6.6 vs 6.4 mm, p = ns, left 6.9 vs 6.6 mm, p = ns) but in common femoral arterial was greater in patients with coronary artery disease (right 8.2 vs 7.1 mm, p < 0.005, left 7.9 vs 7.1 mm, p = 0.03). Atherosclerotic plaques in carotid and femoral arteries was detected more often in CAD patients (90.1% vs 34.6%, p < 0.0001). Positive predictive value for CAD diagnosis with detection of plaque in carotid or femoral artery was 93% and negative prognostic value for exclusion CAD after plaque exclusion in all arteries was 61%. Search for atherosclerotic plaques in ultrasound examination of peripheral arteries may facilitate CAD diagnosis in selected patients groups.     

Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse

Most previous studies of atherosclerosis in hyperlipidemic mouse models have focused their investigations on lesions within the aorta or aortic sinus in young animals. None of these studies has demonstrated clinically significant advanced lesions. We previously mapped the distribution of lesions throughout the arterial tree of apolipoprotein E knockout (apoE(-/-)) mice between the ages of 24 and 60 weeks. We found that the innominate artery, a small vessel connecting the aortic arch to the right subclavian and right carotid artery, exhibits a highly consistent rate of lesion progression and develops a narrowed vessel characterized by atrophic media and perivascular inflammation. The present study reports the characteristics of advanced lesions in the innominate artery of apoE(-/-) mice aged 42 to 60 weeks. In animals aged 42 to 54 weeks, there is a very high frequency of intraplaque hemorrhage and a fibrotic conversion of necrotic zones accompanied by loss of the fibrous cap. By 60 weeks of age, the lesions are characterized by the presence of collagen-rich fibrofatty nodules often flanked by lateral xanthomas. The processes underlying these changes in the innominate artery of older apoE(-/-) mice could well be a model for the critical processes leading to the breakdown and healing of the human atherosclerotic plaque.     

颈动脉粥样硬化斑块成分与性别的相关性研究

目的探讨颈动脉粥样硬化患者斑块成分的性别差异。方法选取进行颈动脉3.0T MR高分辨扫描的颈动脉粥样硬化斑块患者154例,男性95例,女性59例,根据MR扫描结果,对斑块成分和性质进行分析,比较男、女性的斑块成分差异。结果男性斑块内富脂质坏死核(42.1%vs 20.0%,P=0.005)和薄或破裂纤维帽(59.7%vs39.5%,P=0.046)的发生率明显高于女性;女性斑块内钙化的发生率有高于男性的趋势(74.6%vs 65.3%,P=0.225),男性与女性斑块内出血发生率比较,差异无统计学意义(24.2%vs 22.0%,P=0.756)。结论颈动脉粥样硬化斑块患者中,男性不稳定斑块的发生率高于女性,这可能有助于解释脑卒中发病率的性别差异。     

缺血性脑血管病患者颈内动脉斑块的形态学研究

目的　探讨缺血性脑血管病患者和对照组颈内动脉斑块的形态学差异。方法　对 8例有缺血性脑血管病症状的死者进行尸体解剖 ,并对其颈内动脉进行连续取材 ,光镜观察斑块形态 ,并通过图像分析系统对斑块内脂质大小、斑块纤维帽厚度进行测定。同时对 8例年龄相当的无缺血性脑血管病症状的死亡病例 ,做颈内动脉对照研究。选取部分稳定及不稳定斑块进行免疫组织化学染色 ,观察二者巨噬细胞含量的差异。结果　 8例缺血性脑血管病组共 12 1个颈内动脉取材块中 ,不稳定斑块占 2 1.5 % (2 6 12 1) ;而对照组 10 9个颈内动脉取材块中不稳定斑块仅占11.0 % (12 10 9)。差异有显著性意义 (P <0 .0 1)。纤维帽厚度在有症状组和无症状组分别为 (0 .3± 0 .2 )mm和(0 .5± 0 .3)mm ,差异有显著性意义 (P <0 .0 1)。免疫组织化学显示不稳定斑块中巨噬细胞数量明显多于稳定斑块。结论　缺血性脑血管病患者颈内动脉斑块破裂与血栓形成的机会增加 ,斑块脂质中心越大 ,斑块表面纤维帽越薄 ,巨噬细胞越多 ,则斑块越不稳定 ,越容易破裂导致缺血性脑血管病症状的发生。     

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography.

OBJECTIVES: The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well-established murine model of human atherosclerosis. BACKGROUND: Although the pathologic features that predict plaque rupture at autopsy are well known, the development of a technology to identify these high risk features in vivo is lacking. OCT uses reflected light to provide histology-like images of plaque with higher resolution than competing imaging modalities. Whether OCT can reliably identify the features of an atherosclerotic plaque that define it as vulnerable-thin fibrous cap, large lipid core, and high percent of lipid in the artery-requires further study. METHODS: OCT images of the atherosclerotic innominate artery segments from the apolipoprotein E knockout (apoE(-/-)) mice were recorded and correlated with histology in both in vivo (n = 7) and well as in ex vivo experiments (n = 12). RESULTS: Excellent correlation between the OCT and histology measurements for fibrous cap thickness, lipid core size, and percentage lipid content was found. The fibrous cap thicknesses examined span those of human fibrous caps known to rupture (< 65 microm). Regions of greatest light reflection in OCT images were observed when calcium hydroxy-apatite was scattered in lipid, less in fibrous tissue, and least in lipid. CONCLUSIONS: These findings suggest that OCT holds promise for the identification of features defining vulnerable plaque including fibrous cap thickness, lipid core size, and the percentage of lipid content.     

Effects of insulin sensitizers on plaque vulnerability associated with elevated lipid content in atheroma in ApoE-knockout mice

Abstract. Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin (p<0.05) and glucose disposal (p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.     

Lack of association between carotid intima-media thickness and apolipoprotein (a) isoforms in a sample of Spanish general population

ObjectivesThe purpose of this study was to examine the relationship between apolipoprotein (a) isoforms and early atherosclerosis, assessed by carotid artery intima-media thickness in a sample of adults of the general population of Burgos, a city in the north of Spain.Design and methodsLipids, lipoprotein (a), number of carotid atherosclerotic plaques, if any, and the intima-media thickness in the far wall of both common carotid arteries by B-mode ultrasound were determined in a group of 171 adults from the general population of Burgos, Spain. Apolipoprotein (a) isoforms were determined in a random subset of 119 subjects.ResultsIncreasing age, male sex, and past personal cardiovascular history were significantly associated with increased left, right, or average intima-media thickness of both carotid arteries in multivariate analysis.No statistically significant association was found between apolipoprotein (a) isoforms and mean carotid intima-media thickness by bivariate or multivariate regression analysis.ConclusionsIn this sample of the general Spanish population, no association was found between apolipoprotein (a) isoforms and carotid artery intima-media thickness.     

联合应用无创影像学技术预警颈动脉不稳定斑块的相关研究

目的应用高分辨率动态对比增强磁共振成像(DCE-MRI),正电子发射断层显像(PET)技术检测患者颈动脉粥样硬化斑块,比较不同斑块成分之间的炎性程度,为早期预警颈动脉粥样硬化提供临床依据。方法选取颈动脉超声下斑块厚度>2mm的患者41例,分别行DCE-MRI和PET检查。以DCE-MRI图像分析结果,依照粥样硬化斑块表面纤维帽(无纤维帽、厚纤维帽、薄纤维帽、纤维帽破裂)或斑块内血管成分(钙化、胶原、脂质、出血),分析不同斑块性质影像学区别。以DCE-MRI为向导标记PET斑块位置,计算局部放射性活度标准化靶-本底比值(TBR),将DCE-MRI及PET对比研究,比较不同成分斑块间炎性反应程度,以鉴别不稳定斑块。结果不同斑块表面纤维帽中:纤维帽破裂TBRmax值最高,无纤维帽TBRmax值最低,两者比较差异有统计学意义(P<0.01);不同斑块成分中TBRmax值由大到小排列为:斑块出血、富含脂质坏死核、斑块胶原、斑块钙化,除斑块胶原与斑块钙化比较无显著差异外,其他斑块血管成分间差异均有统计学意义(P<0.01)。结论 DCE-MRI和PET无创检查技术联合应用,可以用于颈动脉粥样硬化的早期诊断与评估。