血脂异常导致血管内皮细胞的氧化损伤

在正常生理情况下，血管内皮结构完整、功能正常，一方面通过屏障作用阻止低密度脂蛋白（low density lipoprotein，LDL）等大分子物质和单核细胞等血液细胞成分进入动脉内膜，另一方面又通过产生前列腺素（PCI2）等活性因子发挥抗凝、抑制平滑肌细胞增殖等多种功能。血液中大量LDL在内皮下的沉积导致内皮细胞损伤、单核细胞浸润、血小板粘附聚集、刺激血管平滑肌细胞向血管内膜迁移与增殖，巨噬细胞吞噬脂质而形成泡沫细胞，逐渐发展成动脉粥样硬化斑块。因此，保护内皮细胞免受损伤是防治动脉粥样硬化发生发展的关键。     

血管内皮细胞与动脉粥样硬化的关系

血管内皮细胞 (VEC)是介于血液与血管壁之间的屏障 ,其损伤被认为是动脉粥样硬化 (AS)发病的早期关键性环节。Ross指出 ,AS的发生是由于VEC和平滑肌细胞受各种危险因子如病毒、机械损伤、免疫复合物 ,特别是氧化型低密度脂蛋白 (ox LDL)的损伤 ,而使血管局部产生的一种过度的慢     

新生血管形成与动脉粥样硬化

治疗性血管生成通过增加心肌再灌注而提高心功能、降低心肌梗死的发生率,曾被认为是治疗冠心病的新策略。但是,其给斑块的进展和稳定性带来的一些负面的影响也是不容忽视的。近年来,随着人们对斑块与新生血管形成的关系的认识增多,又有了抑制斑块内新生血管生成而抑制斑块进展和增加斑块稳定性的治疗理念。本文将综述新生血管与动脉粥样硬化斑块稳定性的关系以及抑制新生血管形成的治疗进展。     

血管内皮细胞损伤与高血压

近年来很多研究表明内皮细胞损伤导致的功能障碍与多种心血管疾病的发生发展有着密切相关,包括高血压、冠状动脉性心脏病、糖尿病等。深入探讨血管内皮细胞损伤的机制、评估,保护和修复内皮细胞功能,对改善心血管疾病的预后有积极的意义。现就血管内皮细胞损伤引起的内皮功能障碍和高血压发病机制之间的关系进行综述。     

血管内皮细胞的剪切应力信号转导机制与动脉粥样硬化

剪切应力作用于血管内皮细胞可通过激活膜感受器和细胞内信号转导而调控基因表达,从而影响血管内皮细胞的功能。剪切应力的改变与动脉粥样硬化的发生发展有密切关系。本文就血管内皮细胞的剪切应力信号转导机制及与动脉粥样硬化的关系进行综述。     

蜈蚣对动脉粥样硬化家兔血管内皮细胞生长因子的影响

目的：从内皮细胞功能角度探讨中药蜈蚣对动脉粥样硬化（AS）家兔一氧化氮（NO）、内皮素（ET）以及血管内皮细胞生长因子（VEGF）表达的影响。方法：采用高脂饲喂家兔，建立动脉粥样硬化模型。随机分为4组，每组8只，造模过程中预防性给予蜈蚣治疗。（1）对照组：基础饲料＋5mg/kg蒸馏水灌胃；（2）模型组：高脂饲料＋5mg/kg蒸馏水灌胃；（3）蜈蚣小剂量组：高脂饲料＋蜈蚣水提物2．5g/kg灌胃；（4）蜈蚣大剂量组：高脂饲料＋蜈蚣水提物5g/kg灌胃。4组均饲喂12周。观察血清NO、ET的变化，采用流式细胞术及免疫荧光技术检测VEGF的表达量，并观察其主动脉血管病理。结果：模型组VEGF的表达量升高，经5g/kg蜈蚣治疗后，VEGF的表达量明显下调，NO释放增加，ET分泌减少，与模型组比较有统计学意义（P＜0．01）。而2．5g/kg蜈蚣对VEGF的影响无明显变化，表明蜈蚣对AS血管内皮细胞生长因子的影响存在一定的量效关系。结论：蜈蚣可通过调节NO／ET的平衡，从而抑制VEGF的表达，提示蜈蚣具有保护血管内皮细胞，防治内皮细胞增生的作用，揭示了中医血瘀证存在的微观物质基础，为中药蜈蚣抗动脉粥样硬化的临床应用提供了理论依据。     

体外循环对血管内皮细胞的急性损伤

目的观察体外循环（CPB）对全身血管内皮的急性损伤/活化。方法实验分组:Ⅰ组:60例先天性心脏病心内畸形矫治术患者;Ⅱ组:60例瓣膜病患者。于术中CPB前、CPB 30 min、CPB后0、4、24、48、72 h共7个时点采集静脉血,动态观察患者血浆中血栓调节蛋白（thrombomodulin,TM）、血管性假血友病因子（von Willebrand factor,vWF）、内皮素-1（endothelin-1,ET-1）和一氧化氮（nitric oxide,NO）的变化。结果与CPB前相比,Ⅰ、Ⅱ组患者TM、vWF在CPB 30 min显著升高,CPB结束时升至最高点[TM:（5.7±1.3）μg/Lvs（6.6±1.0）μg/L;vWF:（18±3）μkat/Lvs（23±4）μkat/L,均P<0.01],而后下降,但CPB后72 h仍未恢复到CPB前水平（P<0.05）。ET-1在整个过程中先降后升,与CPB前相比[Ⅰ组:（92±5）ng/L,Ⅱ组:（106±6）ng/L],CPB后4h降至最低[Ⅰ组:（70±5）ng/L,Ⅱ组:（78±3）ng/L,均P<0.01],而后逐渐上升,CPB后72 h明显高于CPB前[Ⅰ组:（101±7）ng/L,Ⅱ组:（122±7）ng/L,均P<0.01]。NO含量在CPB后4 h降至最低水平[Ⅰ组:（42±6）μmol/L,Ⅱ组:（43±5）μmol/L],CPB后72h NO含量[Ⅰ组:（58±6）μmol/L,Ⅱ组:（62±10）μmol/L]恢复至CPB前水平[Ⅰ组:（57±6）μmol/L,Ⅱ组:（63±7）μmol/L]。结论CPB可导致血管内皮细胞的广泛损伤/活化,这种损伤大约72h恢复。     

血管内皮细胞损伤与肾小球疾病

内皮细胞损伤是血管病变的始动环节。高血压、糖尿病、代谢综合征等疾病导致的血管病变已受到广泛关注,但目前肾脏疾病与内皮细胞损伤之间的关系仍未受到足够重视。引起肾脏病患者血管内皮细胞损伤主要包括免疫因素和非免疫因素两个方面,包括免疫炎症反应、高血压、     

血管内皮细胞与再灌流损伤

血管内皮细胞与再灌流损伤上海第二医科大学附属仁济医院心胸外科魏刘华综述朱洪生审校内皮被认为是一个内分泌器官。正常情况下可分泌多种物质来调节血管张力，维持血液的流动性。主要的两种扩血管物质为内皮细胞衍生的松弛因子（ＥＤＲＦ）和前列环素（ＰＧＩ２）。近年...     

Lovastatin prevents the impairment of endothelium dependent relaxation and inhibits accumulation of cholesterol in the aorta in experimental atherosclerosis in rabbits

STUDY OBJECTIVE--The aim was to determine the effect of the HMG CoA reductase inhibitor, lovastatin, on the loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta produced by feeding a diet enriched with cholesterol. DESIGN--The study was conducted in two stages. In stage 1, New Zealand white rabbits were randomised into four groups. Group 1 (n = 15) was fed standard rabbit diet for 6 weeks. Groups 2 (n = 15), 3 (n = 12), and 4 (n = 12) were fed standard rabbit diet supplemented with 2% cholesterol for 2 weeks followed by standard rabbit diet only for the next 4 weeks. In addition, lovastatin (4 mg.kg-1.d-1) was given for the entire 6 weeks in group 3 and for the first 2 weeks only in group 4. In stage 2 a second group of animals was fed a diet supplemented with 0.5% cholesterol for 2 weeks in order to match the serum cholesterol levels in groups 3 and 4 of stage 1. EXPERIMENTAL MATERIAL--Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation (to acetylcholine), contractile responses (to noradrenaline), relaxant responses (to sodium nitrite), and sudan staining. Serum was obtained for measurement of cholesterol and triglyceride concentrations. MEASUREMENTS AND MAIN RESULTS--In stage 1, at the end of 2 weeks, the serum cholesterol was significantly lower in groups 3 and 4 than in group 2. At 6 weeks, endothelium dependent relaxation to acetylcholine (-6.0 log mol.litre-1) was impaired in group 2 compared to the other groups: group 1 78.5(SEM 5.0); group 2 43.5(7.8)%; group 3 79.4(4.6)%; group 4 84.7(3.4)%. The relaxant response to sodium nitrite was not impaired in group 2. Further, the aortic tissue cholesterol concentration in group 2 was significantly greater than that in group 1, at 355(65) v 105(10) nmol.mg-1 protein. In groups 3 and 4, the aortic cholesterol concentrations were significantly lower than those in group 2, at 74(4) and 94(17) nmol.mg-1 protein respectively. In stage 2, the serum cholesterol values were matched to those in groups 3 and 4 of stage 1. In these animals, after a further 4 weeks the aortic cholesterol was significantly greater than in group 3. CONCLUSIONS--Lovastatin attenuates the accumulation of cholesterol and preserves endothelium dependent relaxation in this model of experimental atherosclerosis. It is likely that the latter is a secondary phenomenon.     

颈动脉粥样硬化与血管性认知损害

颈动脉粥样硬化（carotid atherosclerosis, CAS）与老年人认知功能下降密切相关,可导致持续性或进展性认知功能和神经功能障碍。血管性认知损害（vascular cognitive impairment, VCI）被认为是一种可干预疾病。研究显示,CAS是VCI的主要病因之一,进一步研究两者的关系,...     

木贼对动脉粥样硬化早期大鼠内皮细胞凋亡及Bax、Bcl-2表达的影响

目的 观察木贼对大鼠动脉粥样硬化早期血管内皮细胞凋亡及bax、bcl—2表达的影响。方法 高脂饲料复制SD大鼠高脂血症和早期动脉粥样硬化模型，同时给以不同剂量木贼水煎刑灌胃，实验10w后，流式细胞术定量检测各组主动脉内皮细胞凋亡率及bax、bcl—2基因蛋白表达。结果 模型组内皮细胞凋亡率及两个基因表达明显高于正常组(P＜0．01)；木贼组内皮细胞凋亡率与bax表达量显著低于模型组(P＜0．01)，bcl—2比较虽无统计学意义，但用药后bax／bcl—2比值差异具有显著性。结论 木贼可从基因水乎调控早期动脉粥样硬化主动脉内皮细胞凋亡，干预动脉粥样硬化始动环节及其发生。     

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.Improving the design of nanomedicines is key for their success and ultimate clinical application (1). The accumulation of such therapeutic or diagnostic nanomaterials primarily relies on enhanced endothelial permeability of the microvasculature in diseased tissue (2). This holds true for a wide range of pathological conditions, including inflammation, atherosclerosis, and most notably, oncological disease (3–6). Although attributed to the enhanced permeability and retention (EPR) effect, the exact mechanism by which nanoparticles accumulate in tumors continues to be a topic of research (7, 8). The “leaky” vasculature of tumors, which facilitates the extravasation of nanoparticles from microvessels (9), is a heterogeneous phenomenon that varies between different tumor models and even more so in patients. Moreover, the exploitation of nanomedicines in other conditions with enhanced microvessel permeability has only recently begun to be studied in detail. For example, in the last 5 y, a small but increasing number of preclinical studies that apply nanoparticle therapy in atherosclerosis models has surfaced (10). Although several targeting mechanisms have been proposed (4), the exact mechanism by which nanoparticles accumulate in atherosclerotic plaques remains to be investigated, but is likely facilitated by highly permeable neovessels that penetrate into the plaque from the vasa vasorum (Fig. 1A), a network of microvessels that supplies the wall of larger vessels (11).Open in a separate windowFig. 1.Development of an endothelialized microfluidic device to probe nanoparticle translocation over a permeable microvessel. (A) Schematics of continuous normal capillaries surrounding the vessel wall as well as permeable capillaries that penetrate into the atherosclerotic plaque from the vasa vasorum. (B) Schematic of an endothelialized microfluidic device that consists of two-layer microfluidic channels that are separated by a porous membrane (3 μm pore) on which ECs are grown. (C) TEER was dynamically measured across the endothelial layer on the membrane between the upper and lower channels. (D) A well-established monolayer of the microvascular endothelium is formed at TEER ∼400 (Ω·cm²). (E) The monolayer becomes highly permeable when stimulated with the inflammatory mediator, TNF-α, as well as with shear stress, with disruption of intercellular junctional structures (i.e., adherens junctions) between ECs, as evidenced by patchy expression of VE–cadherin (green) in the image on the right versus the left. Blue depicts nuclei stained with DAPI. (Scale bar, 20 μm.) (F) FITC–albumin translocation through the endothelial monolayer increases when the chip is treated with TNF-α. (G) The chip with endothelium cultured in different culture media [base, +FBS, +growth factors (GFs)] for 6 h shows a decrease in TEER with increased FITC–albumin translocation. No cell indicates the membrane only. TEER was normalized to the level with no cells (membrane only). (H) Schematic and TEM image of PEGylated lipid-coated nanoparticles encapsulating PLGA-conjugated AuNCs and Cy5.5. The average size was 69.7 ± 14 nm, which was measured from TEM images. (Scale bar, 100 nm.) Details on labeling, synthesis, characterization, and large-scale production procedures can be found in Materials and Methods and Fig. S2.Advances in biomedical imaging allow the study of plaque-targeting nanoparticles in a dynamic fashion with exceptional detail (12, 13). Microchip technology has the potential to monitor nanoparticle behavior at the (sub)cellular level. Microfluidic chips in which endothelial cells (ECs) are grown in the channels can serve as unique in vitro test systems to study microvascular function and associated disorders (14–18). They allow the isolation of specific biological hallmarks relevant to nanoparticle accumulation, such as the leaky endothelium. In the current study, we validate the potential utility of our microchip technology to study nanoparticle translocation over the endothelium and combine this with in vivo and ex vivo multimodality imaging studies on a rabbit model to better understand nanoparticle targeting of atherosclerotic plaques.     

动脉粥样硬化与血管性认知障碍的相关性研究进展

［摘要］　认知功能障碍是指由多种原因造成的以学习能力和知识应用能力受损为主要临床表现的一类综合征,同时会伴有情绪和精神行为异常,严重危害中老年人的健康。脑血管病变或脑血管病危险因素引起的认知功能障碍被称为血管性认知障碍,研究表明动脉粥样硬化是血管性认知障碍的主要危险因素之一。该文从动脉粥样硬化与血管性认知障碍的相关性、病理机制、治疗以及预防等方面作一综述。     

颈动脉粥样硬化与血管性认知障碍相关性研究

目的 探讨颈动脉粥样硬化与血管性认知障碍的关系。方法 选取2005年5月至2007年4月我院军职干部科疗养干部58例，所有研究对象均进行神经心理检查和颈动脉超声检查，根据颈动脉内膜-中层厚度（IMT）值，将研究对象分为3组：IMT〈1．0mm组、IMT 1．0～1．2mm组和IMT〉1．2mm组，并对不同组的神经心理检查结果进行分析。结果 不同颈动脉粥样硬化患者日常生活能力比较无显著性差异（P〉0．05）。简易智能状态检查量表总分各组间比较无显著性差异。地点定向、时间定向、计算能力、短程记忆、言语复述、语言表达、书写能力、结构能力评分，IMT〉1．2mm组得分明显较低，3组间比较有显著性差异（P均〈0．05）。结论 颈动脉粥样硬化与血管性认知障碍存在密切的关系。