动脉粥样硬化斑块内血管新生的研究进展

斑块内血管新生在动脉粥样硬化的发生发展中可能是一个核心事件并起着关键性作用 ,进一步研究新生血管的发生机制及其病理生理意义并寻求较佳的防治方法 ,可以为认识动脉粥样硬化的发病机制和防治动脉粥样硬化提供一个新的视点。     

斑块内新生血管的作用及应对

斑块内新生血管是由内皮细胞芽生形成.动脉粥样硬化相关的生理性新生血管能改善动脉壁供氧状态,减轻炎症反应,逆转动脉粥样硬化的进展.病理性新生血管则会加速疾病的进程,增加巨噬细胞浸润和血管壁的厚度,导致持续的缺氧状态,甚至坏死.此外,新生血管壁的破裂可以导致斑块内出血、增强炎性反应、扩大脂质核心、激发氧化应激反应和斑块破裂.     

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。     

新生滋养血管在动脉粥样硬化斑块进展中的作用

滋养血管新生作为动脉粥样硬化斑块发生发展中的关键环节已受到普遍关注,在动脉内膜发生缺血缺氧或炎症时可诱发滋养血管新生,并通过白细胞征募和斑块内出血等机制影响斑块的稳定性.     

动脉粥样硬化斑块内血管新生与中医药干预现状

动脉粥样硬化(atherosclerosis,As)是严重危害人类生命健康的疾病之一,其发病率和死亡率均居各种疾病前列[1],它不仅是动脉自身的疾病,也是导致心肌梗死、脑梗死、坏疽和肢体功能丧失的主要原因[2],是心脑血管病的主要病理基础,是严重影响人类健康的心血管疾病.因此,寻求防治动脉粥样硬化的更有效的方法是医学临床及实验研究者的一个重要任务.近年发现的动脉粥样硬化斑块内新生血管可影响斑块稳定性,已有许多学者正努力地进行更进一步研究,现从新生血管影响斑块稳定性的机制以及中医在这方面所取得的研究进展等方面进行概述.     

超声造影评价颈动脉斑块内新生血管的研究进展

动脉粥样硬化斑块与心脑血管事件的发生密切相关,早期评估动脉粥样硬化斑块的稳定性对于预防心脑血管事件发生及制定治疗方案十分重要。大量研究证实斑块内新生血管与斑块的稳定性有关,超声造影可显示和评估颈动脉斑块内新生血管,是近年来斑块稳定性研究的热点技术之一。     

支架内新生动脉粥样硬化斑块的研究进展

冠状动脉支架内新生动脉粥样硬化斑块的破裂可能导致晚期支架内血栓形成,引起严重的临床后果。目前关于支架内新生动脉粥样硬化斑块发生发展的机制尚不清楚,临床上尚无有效的干预措施。     

动脉粥样硬化病变处血管新生的病理意义

发生动脉粥样硬化的冠状动脉内膜往往出现血管新生.这些新生血管可以促进粥样硬化病变的发展,甚至诱发斑块出血和斑块破裂.进一步研究新生血管的发生机制及其病理生理意义并寻求较佳的防治方法,可以为认识动脉粥样硬化的发病机制和防治动脉粥样硬化提供一个新的视点.     

动脉粥样硬化斑块滋养血管研究

研究表明,动脉粥样硬化斑块滋养血管在促进斑块的进展、不稳定斑块的形成、斑块内出血甚至破裂方面有着不可忽视的作用。随着对不同阶段斑块滋养血管新生机制研究的进一步深入,针对其进行有效的干预进而达到延缓斑块进展、增加斑块稳定性的目的也将成为可能,这或许能够为临床治疗动脉粥样硬化疾病提供新的策略和理念。     

微小RNA在动脉粥样硬化易损斑块中的研究进展

微小RNA(miRNA)是一类在进化上高度保守的非编码小分子单链RNA(约18～24个碱基),在转录后水平负性调控基因表达。易损斑块是指动脉粥样硬化过程中易于形成血栓或可能迅速进展为罪犯病变的斑块。研究表明,miRNA几乎参与了动脉粥样硬化形成的所有步骤,包括内皮细胞及血管平滑肌细胞损伤和功能障碍、单核细胞浸润及血小板功能障碍,并发挥有益或有害作用。miRNA也将成为深入研究中医药双向调节易损斑块作用机制新的领域。     

MRTF-A在动脉粥样硬化病变中的研究进展

动脉粥样硬化是心血管事件发生的重要因素。相关流行病学调查显示,近几年中国动脉粥样硬化性心血管疾病负担快速而显著增加,给国家公共卫生问题带来重大挑战。心肌素相关转录因子A(MRTF-A)在动脉粥样硬化发展进程中发挥着重要作用,包括参与炎症反应、促进粥样硬化进程中脂质积聚及促进血管平滑肌细胞表型转化等,探索MRTF-A在动脉粥样硬化病变中的研究进展对于寻找新的治疗靶点具有重要意义。文章就MRTF-A在动脉粥样硬化病变过程中的作用进行综述,可为冠状动脉粥样硬化的靶向治疗提供参考。     

Neopterin is associated with plaque inflammation and destabilisation in human coronary atherosclerotic lesions

Background

Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. Neopterin, a by‐product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages.

Objective

To elucidate the role of neopterin in coronary plaque destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).

Patients and methods

All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n = 25) and UAP (n = 25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils and neopterin.

Results

In 22/25 patients with UAP, abundant neopterin‐positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin‐positive macrophage score was significantly higher (p<0.001) in patients with UAP than in patients with SAP. Moreover, the neopterin‐positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, p<0.001; T cells, r = 0.70, p<0.001).

Conclusions

Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.     

粥样斑块发生发展过程中炎症和新生内膜血管之间的关系

目的为研究在控制炎症水平的情况下内膜新生血管在动脉粥样斑块发生、发展中所起到的具体作用。方法高脂饮食8周造成大鼠动脉粥样硬化（AS）模型,然后使用阿司匹林抑制AS大鼠的基础炎症水平,分别给予内皮抑素和血管内皮生长因子165（VEGF165）两种不同方法处理大鼠,8周后比较血脂、胸主动脉形态学、以及检测CD31表达水平以计算内膜新生血管的数量。结果模型组的血脂水平高于空白对照组（P<0.05）;粥样斑块内部的新生血管数量VEGF165+阿司匹林组>单纯模型对照组>阿司匹林组>内皮抑素+阿司匹林组>空白对照组（P<0.05）;阿司匹林组、内皮抑素+阿司匹林组和VEGF165+阿司匹林组的内膜面积/中膜面积的比值（IA/MA）差异无显著性,但高于单纯模型对照组（P<0.05）。结论在用阿司匹林抑制AS模型大鼠基础炎症的情况下,VEGF165和内皮抑素对血管内膜生成的影响无显著差异。     

生物标志物在动脉粥样硬化相关性脑卒中的研究进展

动脉粥样硬化相关性脑卒中的高发病率、高致残率及高病死率给社会和患者及患者家属带来严重影响,因此,及时有效的诊断对临床医师准确评估病情的危险因素,并选择有效的治疗方法尤为重要。研究表明,越来越多的蛋白、微小RNA及脂质因子的表达变化与动脉粥样硬化相关性脑卒中的发生、发展和预后密切相关,可能是脑卒中潜在生物标志物。本文通过查阅国内外文献,对动脉粥样硬化相关性脑卒中的生物标志物进行了系统的最新综述,为防治动脉粥样硬化相关性脑卒中提供新思路。     

冠状动脉粥样硬化斑块愈合的研究进展

动脉粥样硬化斑块破裂后的愈合过程对临床结果意义重大,良好的斑块愈合可以阻止血栓的进一步发展,避免急性心血管事件的发生,但反复的斑块愈合也被认为可加重斑块负荷,引起血管慢性狭窄。随着腔内影像技术的发展,对斑块愈合的研究愈加深入,许多针对斑块愈合的治疗方法也在实施或研究中。     

长链非编码RNA调节痛风炎症信号通路的研究进展

长链非编码RNA(LncRNAs)是指无蛋白质编码功能、长度大于200个核苷酸的非编码RNA。随着基因测序及基因芯片的快速发展,越来越多的研究表明,LncRNAs可通过调节细胞免疫、表观遗传、基因转录及转录后水平调控基因表达,从而参与人体多种疾病的发病过程。近年来,随着生活习惯、饮食结构的改变,痛风患者日趋增多,有研究显示LncRNAs在痛风发病中尤其是在痛风相关炎症信号通路调控中发挥重要作用。本文就此部分研究进展进行综述,进一步揭示痛风发病机制,以期对痛风及其并发症的早期预防、治疗提供新方法。     

长链非编码RNA在血管生成中的研究进展

生理性的血管生成对于组织修复、机体平衡具有重要的作用,但异常的血管生成可诱发多种疾病,如癌症、缺血性心脏病、中风等。调节血管的生成对于诸多疾病的治疗具有重要意义,抗血管生成疗法已在某些疾病中显示了治疗意义,但促血管生成疗法仍然是一个难题。近年来,大量研究显示长链非编码RNA(lncRNA)在血管生成中扮演着重要的角色,通过调节异常的lncRNA,可以抑制或促进血管生成,这为治疗异常血管生成的相关疾病开辟了新的领域。     

Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and seruminflammatory cytokines in atherosclerotic rabbit model

Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P＜0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2.18±0.17 vs 1.58±0.22,1.22±0.15,P＜0.001,respectively).The expression in physiological stress subgroup was higher than that in no-stress subgroup (584±0.22 vs 1.22±0.15,P=0.001).(2) The serum level of IL-6 (51.80±4.60 pg/ml vs 27.60±4.19 pg/ml,8.01±1.39 pg/ml,7.83±1.37 pg/ml),sICAM-1 ( 1.24±0.25 vs 0.85±0.09,0.62±0.17,0.57±0.11),CRP ( 1.004±0.37 vs 0.90±0.29,1.01±0.22,0.71±0.13) in psychological stress group were significantly higher than that in other groups (All P＜0.05).There was a positive relationship between the serum level of CRP,IL-6 and ICAM-1 and the expression of ICAM-1 in aorta wall ( r =0.59,r =0.75,r =0.87,P＜0.01,respectively).Conclusions Psychological stress induces an increased expression of ICAM-1 in aortic atherosclerotic plaque,a higher serum level of CRP,IL-6,and sICAM-1 expression.Psychologial stress has a direct effect on the transition from stability to unstability through in-plaque and out-plaque inflammation.The serum level of CRP,IL-6 and ICAM-1 can reflex the inflammatory degree in atherosclerotic plaque.(J Geriatr Cardiol 2008;5:235-242)