动脉粥样硬化斑块内新生微血管的研究进展

血管新生是在已存在的毛细血管基础上以芽生或非芽生方式生成新的毛细血骨的生理或病理过程.在生理状态下,新生血管由内皮细胞及壁细胞(包括周细胞和血管平滑肌细胞)组成,包埋在细胞外基质,因此结构比较稳定,不易渗漏.     

Adiponectin and vulnerable atherosclerotic plaques

High-risk plaques that are vulnerable to rupture demonstrate distinct morphological characteristics. They are differentiated from the lesions responsible for stable coronary artery disease by their large necrotic cores, thin-inflamed fibrous caps, and positive remodeling. Adiponectin is an adipocytokine that is reduced in obesity and type 2 diabetes. Hypoadiponectinemia has been associated with an increased risk of coronary artery disease and acute coronary syndrome in several though not all studies. The involvement of adiponectin provides clues to the inflammatory and atherogenic mechanisms associated with pathological coronary disease progression.     

Metalloproteinases and vulnerable atherosclerotic plaques

Plaque rupture is the main cause of myocardial infarctions and strokes. Ruptured plaques have thin, highly inflamed, and collagen-poor fibrous caps that contain elevated levels of proteases, including metalloproteinases (MMPs), which might weaken plaque caps and promote rupture. On the other hand, MMPs facilitate migration and proliferation vascular smooth muscle cells, which should promote fibrous cap stability. Given the dual effects of MMPs, therapies should selectively target harmful MMPs or the processes that cause MMP activity to rise to destructive levels.     

他汀类药物对动脉粥样硬化斑块稳定与消退的作用

动脉粥样硬化斑块破裂是动脉粥样硬化相关性缺血性卒中(AT-IS)的主要发病机制。而通过医学干预使粥样硬化斑块保持稳定甚至消退,则是针对AT-IS进行一级和二级预防治疗的新靶点,也是标志其预防是否成功的关键。动物研究发现,炎症不仅贯穿于动脉粥样硬化的形成与进展、粥样硬化斑     

颈动脉粥样硬化斑块的形态学及炎性反应与临床表现的观察

目的评价颈动脉粥样硬化斑块形态学变化、炎性反应及其与临床症状的关系。方法选择9例症状性颈动脉粥样硬化性狭窄患者,通过经颅多普勒超声检测,示4例患者有栓子脱落,5例无栓子脱落。对患者均行颈内动脉内膜切除术,取动脉粥样硬化斑块标本,一部分行常规HE染色,观察常规形态学改变;另一部分做免疫组化染色,观察CD3、CD45RO、CD20、α-平滑肌肌动蛋白(α-SMA)及增殖细胞核抗原(PCNA)的表达情况;并观察炎性细胞浸润程度与栓子脱落的关系。结果①光镜下结果显示,在斑块的肩部和纤维帽内可见一些新生小血管、不同程度的炎性细胞浸润及平滑肌细胞减少。炎性细胞主要分布在新生小血管周围,血管增生越明显,浸润的炎性细胞越多,平滑肌细胞减少越明显。②免疫组化染色结果显示,浸润的炎性细胞为CD3和CD45RO染色阳性的T淋巴细胞,主要分布在新生小血管周围;α-SMA在斑块纤维帽内的表达呈不均匀性,部分区域没有表达。PCNA染色呈阳性,证实细胞增殖处于活跃期。③有栓子脱落患者的颈动脉粥样硬化斑块具有更明显的炎性细胞浸润。结论在颈动脉粥样硬化斑块内,以T淋巴细胞为主的炎性反应对斑块的不稳定性起重要作用。     

中介素1-53与高血压颈动脉粥样硬化斑块形成之间的相关性

目的探讨中介素1-53与高血压颈动脉粥样硬化斑块形成之间的相关性。方法随机收集在本院就诊的1~2级高血压患者138例,进行颈动脉超声检查,根据结果分为斑块组98例和无斑块组40例,另选同期健康体检者30例为对照组,分别检测血浆中介素1-53水平,比较各组血压、颈动脉内膜中层厚度(cIMT)及中介素1-53水平。结果斑块组和无斑块组患者的诊室收缩压[(158.57±13.55)mm Hg、(145.16±14.54)mm Hg vs(125.24±10.64)mm Hg,1mm Hg=0.133kPa]、舒张压[(95.23±5.62)mm Hg、(87.15±4.72)mm Hg vs(80.31±4.62)mm Hg]、cIMT[(1.26±0.38)mm、(1.05±0.28)mmvs(0.87±0.38)mm]及中介素1-53水平[(7.20±1.62)ng/L、(5.05±1.85)ng/L vs(3.06±1.01)ng/L]高于对照组(P0.05,P0.01),且斑块组患者中介素1-53水平较无斑块组更高,差异有统计学意义(P0.01)。结论中介素1-53可能参与颈动脉粥样硬化斑块的形成,有抵抗或延缓颈动脉粥样硬化斑块形成的作用。     

Vasa vasorum imaging: A new window to the clinical detection of vulnerable atherosclerotic plaques

Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so forth) lead to heart attacks and strokes. It remains difficult to identify what plaques are vulnerable to these complications. Despite recent developments such as thermography, spectroscopy, and magnetic resonance imaging, none of them is approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet widely available clinical tool for guiding intracoronary procedures, is increasingly used for characterization of atherosclerotic plaques. However, inability of IVUS in measuring plaque activity limits its value in detection of vulnerable plaques. In this review, we present new information suggesting that microbubble contrast-enhanced IVUS can measure activity and inflammation within atherosclerotic plaques by imaging vasa vasorum density. An increasing body of evidence indicates that vasa vasorum density may be a strong marker for plaque vulnerability. We suggest that a combination of structural assessment (cap thickness, lipid core, calcification, etc) and vasa vasorum density imaging by IVUS can serve as the most powerful clinically available tool for characterization of vulnerable plaques. Due to space limitations, all IVUS images and movies are posted on the website of the Ultimate IVUS Collaborative Project: http://www.ultimateivus.com     

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques

Background Atherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract (GSPE) has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use. Methods Consecutive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness (CIMT) were randomly assigned to the GSPE group (n = 146) or control group (n = 141). The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was performed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT (MMCIMT), plaque score, echogenicity of plaques and ischemic vascular events were recorded. Results As anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT progression (4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months) and plaque score (10.9% decrease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months) for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also decreased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack (TIA), arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower (P = 0.02, 0.08, 0.002, respectively) compared with the control group. Conclusions GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.     

Carotid and femoral atherosclerotic plaques show different morphology

TRAIL (tumour necrosis factor-related apoptosis inducing ligand) is most often reported to induce apoptosis in tumour cells. It is expressed in artery walls but its role and regulation in vascular pathologies is little studied. We aimed to measure the effect of genetic deletion of TRAIL on atherosclerosis in a mouse model. TRAIL was mainly expressed in endothelium, smooth muscle cells and macrophages within plaques. The absence of TRAIL in chow and in fat-fed mice led to greater lesion coverage in aortae (8 weeks, % area ± SEM), n=7-8, 1.24 ± 0.2 (no TRAIL, chow diet) vs. 0.42 ± 0.1, p<0.01 and 3.4 ± 0.8 (no TRAIL, Western diet) vs. 0.94 ± 0.2, p<0.01 and larger, smooth muscle cell rich lesions at aortic roots than control mice (8 weeks, mean lesion area/total cross sectional area ± SEM, n=7-8, 0.17 ± 0.01 (no TRAIL, chow diet) vs. 0.135 ± 0.006, p<0.05 and 0.36 ± 0.03 (no TRAIL, Western diet) vs. 0.23 ± 0.02, p<0.05) particularly at early time points. The larger early lesions appeared to be as a result of increased smooth muscle cells in lesions of TRAIL deficient, pro-atherosclerotic animals. We conclude that TRAIL attenuates plaque size at early stages of atherosclerosis.     

颈动脉粥样硬化斑块影像学评估研究进展

对于颈动脉斑块的评估,经典的策略是通过影像学进行狭窄程度分级,从而决定临床干预方式。而随着临床经验和研究证据的积累,人们逐渐认识到斑块稳定性这一指标比狭窄程度更能准确反映患者的症状和预后、评估再血管化指征。本文整合了近年来经典或新型影像技术(超声、计算机断层扫描、磁共振、分子成像等)的研究进展,分析了这些技术在斑块形态及稳定性方面评估的原理和优劣,为临床提供参考。     

Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation

Background—Unstable angina is a heterogeneous clinical syndrome. The diverse clinical presentations of unstable angina may reflect different pathogenic mechanisms within the plaque.
Objective—To investigate the cellular constituents of culprit coronary atheromatous plaques in patients with stable angina pectoris and patients with diverse clinical presentations of unstable angina.
Methods—48 patients who underwent coronary atherectomy for management of ischaemic heart disease: 23 had stable angina and 25 had unstable angina. Of the latter, 11 patients were classified as Braunwald''s IIB and 14 as Braunwald''s IIIB unstable angina. The presence of thrombus, cholesterol clefts, and smooth muscle cell proliferation was assessed in atherectomy samples using standard histological techniques. Monoclonal antibodies were used to identify smooth muscle cells and macrophages within atherosclerotic plaque fragments.
Results—Fresh thrombus was more frequently found in patients with Braunwald''s IIIB unstable angina (64%) than in patients with stable angina (22%) or IIB unstable angina (27%) (p < 0.0006). A pattern of smooth muscle cell proliferation ("accelerated progression pattern") was observed which was also associated with coronary thrombus. This pattern was present in 30% of patients with stable angina, 64% of patients with IIIB unstable angina, and in all patients (100%) with IIB unstable angina. Atherosclerotic plaques with thrombus, cholesterol clefts, and macrophages were more common in patients with unstable angina than in stable angina patients.
Conclusion—The presence of a specific smooth muscle cell proliferation (accelerated progression) pattern in patients with unstable angina, particularly in those with Braunwald''s IIB unstable angina, suggests that episodic plaque disruption and subsequent healing may be an important mechanism underlying angina symptoms in these patients.

     

急性心肌梗死与颈动脉粥样硬化斑块关系的研究

目的 探讨急性心肌梗死与颈动脉粥样硬化斑块的相关性.方法 选择急性心肌梗死患者(AMI组)30例及非急性心肌梗死患者(对照组)28例进行颈动脉超声检查,并记录粥样硬化斑块(尤其是不稳定型斑块)的发生及超声特征情况.对两组病例的斑块发生率进行统计学分析.结果 急性心肌梗死组颈动脉斑块发生率为83.33%,对照组为57.1...