姜黄素通过影响巨噬细胞的极性延缓动脉粥样硬化进展

目的研究姜黄素对ApoE基因敲除(ApoE~(-/-))小鼠动脉粥样硬化进展及斑块中巨噬细胞极性的影响。方法用高脂高胆固醇饮食饲养ApoE~(-/-)小鼠建立动脉粥样硬化模型,设立姜黄素治疗组、阿托伐他汀治疗组和高脂组;通过免疫组织化学(HE染色、油红O染色、Masson染色、苏木精染色)及免疫荧光染色检测主动脉斑块形态及不同亚型巨噬细胞的含量。通过实时荧光定量PCR检测主动脉组织中炎症因子的表达。结果姜黄素干预能减轻ApoE~(-/-)小鼠主动脉粥样硬化病变,并降低动脉粥样硬化斑块的易损指数。姜黄素降低动脉粥样硬化斑块内M1/M2巨噬细胞的比值,减少M1型巨噬细胞分泌的促炎因子白细胞介素1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子α(TNF-α)的表达,促进M2型细胞因子IL-10、Ym1和Fizz1的表达。结论姜黄素可通过影响斑块中巨噬细胞的极性、抑制相关的炎症反应,从而延缓ApoE~(-/-)小鼠动脉粥样硬化的进展。     

神经导向因子Netrin-1调节单核巨噬细胞迁移与动脉粥样斑块关系的研究进展

动脉粥样硬化是动脉壁的一种慢性炎症性疾病,单核巨噬细胞在其发生发展中起着关键作用。动脉粥样斑块中单核巨噬细胞迁移能力受损,滞留于斑块内,增加了斑块不稳定性,加速动脉粥样硬化病变的进展。目前研究表明动脉粥样斑块中巨噬细胞分泌的神经导向因子Netrin-1通过与巨噬细胞表面相应受体结合,可以抑制巨噬细胞迁出斑块,促进动脉粥样硬化的进展。但在动脉粥样硬化形成初期,血管内皮细胞表达的Netrin-1却被发现对动脉粥样硬化起到保护作用。     

老年患者股动脉和颈动脉及冠状动脉粥样硬化斑块稳定性的比较

目的　探讨股动脉、颈动脉、冠状动脉粥样硬化斑块的稳定性。方法　收集我院老年尸体解剖病例 15例 ,将所有病例的两侧股动脉、两侧颈动脉、左冠状动脉前降支进行连续取材 ,常规病理检查 ,部分节段行α 平滑肌肌动蛋白、CD6 8、bax染色。结果　股动脉粥样硬化斑块中的平滑肌细胞、巨噬细胞数量与颈动脉相近。与冠状动脉比较 ,股动脉粥样硬化斑块中的平滑肌细胞相对多 ,巨噬细胞相对少 ;bax在巨噬细胞的表达多 ,在平滑肌细胞的表达少。结论　平滑肌细胞、巨噬细胞数量的不同导致了 3种动脉粥样硬化斑块不同的稳定性。股动脉中的粥样硬化斑块较冠状动脉更稳定。     

巨噬细胞、血管平滑肌细胞与冠状动脉粥样硬化易损斑块的相关性研究

冠状动脉动脉粥样硬化是冠心病的病理基础,以血管壁斑块形成为特征.易损斑块定义为易于导致血栓形成或能迅速发展为罪犯病变的所有斑块,其最常见的组织学亚型具有薄纤维帽(厚度＜65μm)、大脂核(脂质池体积＞40％)、大量巨噬细胞浸润(显微镜下＞25个/0.3mm直径)以及血管正性重构等特点.研究表明,65％～70％的血栓南薄纤维帽粥样硬化斑块引起[1],它的破裂是急性冠脉综合征的发病基础.冠状动脉动脉粥样硬化的各种发病机制均与巨噬细胞和血管平滑肌细胞有紧密关系.在易损斑块中,这两种细胞成分明显有别于稳定斑块以及正常血管,主要表现为:(1)较多巨噬细胞浸润;(2)纤维帽中的血管平滑肌细胞及其分泌的细胞外基质(包括胶原纤维和蛋白多糖等)均明显减少[2].冠状动脉粥样硬化斑块的易损性与这两种细胞密切相关,故深入研究有助于认识易损斑块的发生机制并积极进行预防干预.我们就巨噬细胞和血管平滑肌细胞与冠状动脉粥样硬化易损斑块的相关性进行简要综述.     

巨噬细胞极化及其衍生微粒在动脉粥样硬化中的作用

巨噬细胞作为动脉粥样硬化(AS)斑块中最主要的炎性细胞,与动脉粥样硬化发展及斑块稳定性密切相关。微粒作为细胞间信息传递的载体,不仅参与诱导巨噬细胞的极化,还参与动脉粥样硬化发展的各个病理环节。现就动脉粥样硬化中巨噬细胞亚型及其衍生微粒的作用进行综述,以期为防治动脉粥样硬化提供新的研究思路和干预靶点。     

动脉粥样硬化进程中单核/巨噬细胞的行为变化

动脉粥样硬化是由脂质引发的炎症性疾病,单核/巨噬细胞在动脉粥样硬化发生发展过程中发挥极其重要的作用。巨噬细胞吞噬脂质后成为泡沫细胞,构成动脉粥样硬化的脂质条纹和粥样斑块。过去几年中,对于单核细胞如何聚集、分化、摄取脂质及其在动脉粥样硬化中的作用有了进一步了解。单核/巨噬细胞表型和功能的复杂性提示其很可能会成为动脉粥样硬化治疗的靶点。本文就单核/巨噬细胞在动脉粥样硬化进程中的行为变化进行综述。     

冠状动脉粥样硬化斑块中巨噬细胞的影像学检查

冠脉粥样硬化斑块的形成给人们健康带来严重危害,而巨噬细胞在斑块形成发展中起着重要作用,成为判断动脉粥样硬化斑块稳定与否的一个重要标志,因此巨噬细胞的识别及定量成为如今研究的热点。本文阐述了目前常用的检测冠脉斑块及其内巨噬细胞的影像学技术。     

巨噬细胞在冠状动脉粥样硬化过程中作用及机制研究现况

动脉粥样硬化发生发展过程机制复杂,损伤应答假说、感染假说、脂质沉积假说、炎症假说等从各自角度阐述了这一过程的可能机制。巨噬细胞是各种假说的中心,在动脉粥样硬化的发生发展过程发挥至关重要的作用。然而,参与动脉粥样硬化的巨噬细胞来源不尽相同,亚型众多,各自发挥不同的作用。此外,巨噬细胞参与动脉粥样硬化的过程包括黏附、聚集、分化、吞噬、炎症、凋亡、自噬、胞葬等多个方面。因此,研究巨噬细胞作用,探索巨噬细胞相关靶点,对指导冠状动脉粥样硬化型心脏病的精准医疗具有重要意义。     

细胞水平胰岛素抵抗导致动脉粥样硬化斑块进展的研究

近期提出细胞水平胰岛素抵抗包括内皮细胞、平滑肌细胞和巨噬细胞,即粥样硬化斑块病变内细胞自身存在胰岛素信号通路的缺陷导致细胞生物学性能的改变,在动脉粥样硬化斑块进展中起关键作用.如斑块内细胞自身胰岛素抵抗可降低内皮细胞的舒张功能、平滑肌细胞的增殖、迁移并增加巨噬细胞凋亡和吞噬缺陷,导致粥样硬化斑块坏死核心的扩大.因此,深入了解细胞水平胰岛素抵抗参与动脉粥样硬化疾病发生、发展的机制为未来研发新型药物开辟新方向.     

不稳定型心绞痛患者中的巨噬细胞平滑肌细胞及组织因子

冠脉粥样硬化斑块破裂及继发血栓形成是导致急性冠脉综合征的最重要机制。既往的研究表明巨噬细胞(M)表达的组织因子(TF)可能是粥样斑块致血栓形成作用的介导因子,而斑块中的平滑肌细胞(SMC)也可能有致血栓形成作用,具体机制不清。本实验旨在研究不稳定型心绞痛患者冠脉粥样斑块组织中TF的分布及其M、SMC的关系。     

巨噬细胞极化与动脉粥样硬化

巨噬细胞是动脉粥样硬化过程中最具代表性的炎症细胞。机体通过多个信号通路选择性表达靶基因,使巨噬细胞呈现相应特征性的分子标志物,最终实现不同极性及功能,即促炎的M1型和抗炎的M2型巨噬细胞。MI/M2型巨噬细胞具有可塑性,二者的分化影响着动脉粥样硬化的发展结局。因此,如何控制巨噬细胞介导的炎症反应已成为心血管领域的关注热点,也为动脉粥样硬化的防治带来新的希望。     

Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo

Objective

Macrophages show extreme heterogeneity and different subsets have been characterized by their activation route and their function. For instance, macrophage subsets are distinct by acting differently under pathophysiological conditions such as inflammation and cancer. Macrophages also contribute to angiogenesis, but the role of various specific subsets in angiogenesis has not been thoroughly investigated.

Methods and results

Matrigel supplemented with macrophage subsets [induced by IFNγ (M1), IL-4 (M2a) or IL-10 (M2c)] was injected subcutaneously in C57BL/6 J mice and analyzed by CD31 staining after 14 days. Increased numbers of endothelial cells and tubular structures were observed in M2-enriched plugs compared to control and other subsets. Additionally, more tubular structures formed in vitro in the presence of M2 macrophages or their conditioned medium. To identify a mechanism for the pro-angiogenic effect, gene expression of angiogenic growth factors was analyzed. Induced expression of basic fibroblast growth factor (Fgf2), insulin-like growth factor-1 (Igf1), chemokine (C–C motif) ligand 2 (Ccl2) and placental growth factor (Pgf) was observed in M2 macrophages. Using a blocking antibody of PlGF to inhibit M2c induced angiogenesis resulted in mildly reduced (40 %) tube formation whereas neutralization of FGF-2 (M2a) signaling by sFGFR1-IIIc affected tube formation by nearly 75 %.

Conclusions

These results indicate that macrophages polarized towards an M2 phenotype have a higher angiogenic potential compared to other subsets. Furthermore, we propose FGF signaling for M2a- and PlGF signaling for M2c-induced angiogenesis as possible working mechanisms, yet, further research should elucidate the exact mechanism for M2-induced angiogenesis.     

巨噬细胞极化在寄生虫感染中的作用研究进展

巨噬细胞是固有免疫的重要成员,在机体防御病原生物感染、肿瘤、过敏性疾病等发生发展中发挥着极其重要的作用。巨噬细胞具有高度可塑性,在不同环境刺激下巨噬细胞可极化为经典活化型巨噬细胞（M1型巨噬细胞）和替代活化型巨噬细胞（M2型巨噬细胞）。M1型巨噬细胞能够促进机体炎症反应,有利于清除病原体;M2型巨噬细胞能够抑制炎症反应,有利于病原体生存、繁殖。本文综述巨噬细胞极化在寄生虫感染中的作用,为寄生虫病防治研究提供参考。     

动脉粥样硬化中巨噬细胞表型调控的研究进展

巨噬细胞是体内的一种吞噬细胞,与动脉粥样硬化病变的发生发展密切相关。研究表明,巨噬细胞的不同表型对动脉粥样硬化的进展发挥着不同作用。此外,减少促炎巨噬细胞亚群的局部增殖以及诱导巨噬细胞向抗炎表型转化是未来动脉粥样硬化治疗的关键。本文就巨噬细胞表型、表型调控相关信号通路及针对巨噬细胞表型调控的相关治疗途径展开综述,以期为动脉粥样硬化的防治提供新的靶点和途径。     

巨噬细胞极化分型与儿童支气管哮喘的相关性分析

目的 探讨巨噬细胞极化分型与儿童支气管哮喘(简称哮喘)演进的相关性并分析其可能相关机制.方法 分离2014年9月至2016年8月两年间西安市儿童医院哮喘患儿外周血中单核巨噬细胞,流式细胞术分析M1与M2的比例,并且分析其与患儿急性发作严重分级的相关性及常规全球哮喘防治创议方案控制疗效的相关性.结果 哮喘患儿急性发作严重分级及控制疗效与外周血中巨噬细胞无相关性(P＞0.05),与M1及M2呈现较强的相关性(P＜0.01),与M1呈正相关(r=0.938),与M2呈负相关(r=-0.835).结论 哮喘患儿外周血中巨噬细胞的不同亚群对该疾病的演进及预后发挥不同的作用,因此巨噬细胞极性的转变有可能成为儿童哮喘治疗的关键节点.     

Making a Difference: Monocyte Heterogeneity in Cardiovascular Disease

Monocytes are frequently described as bone marrow-derived precursors of macrophages. Although many studies support this view, we now appreciate that monocytes neither develop exclusively in the bone marrow nor give rise to all macrophages and dendritic cells. In addition to differentiating to specific leukocyte populations, monocytes, as monocytes, are functionally and ontogenically heterogeneous. In this review we will focus on the development and activity of monocytes and their subsets in mice (Ly-6?C(high/low)) and humans (CD14(+/dim/-) CD16(+/-)) in the context of atherosclerosis and its complications.     

Monocyte and macrophage subsets along the continuum to heart failure: Misguided heroes or targetable villains?

The important contribution of monocytes and macrophages to cardiovascular disease and heart failure pathophysiology has attracted significant attention in the past several years. Moreover, subsets of these cells have been shown to partake in the initiation and exacerbation of several cardiovascular pathologies including atherosclerosis, myocardial infarction, pressure overload, cardiac ischemia and fibrosis. This review focuses on the role of monocytes and macrophages along the continuum to heart failure and the contribution of different cell subsets in promoting or inhibiting cardiac injury or repair. It outlines a primary role for the monocyte/macrophage system as an important regulator of cardiac inflammation and extracellular matrix remodelling in early and late stage heart disease with particular focus on phenotypic plasticity and the inflammatory and fibrotic functions of these cells. It also summarizes evidence from pre-clinical and clinical studies evaluating monocyte type regulation and its functional significance for development of cardiovascular disease and heart failure. Finally, current and prospective therapeutic approaches based on monocyte and macrophage manipulation for the treatment of cardiovascular disease and heart failure are discussed. Based on these data, future work in this fertile research area may aid in identifying potential diagnostic biomarkers and novel therapies for chronic heart failure.     

Myeloid cells in cardiovascular organs

Myeloid cells assume a wide range of phenotypes, some of which are protective against injury and infection whilst others promote cardiovascular disease. This heterogeneity is partially caused by switching of cell sources from local tissue‐resident macrophage proliferation to recruitment of circulating cells, and partially due to macrophages’ phenotypic plasticity. While long‐lived tissue‐resident macrophages support development, tissue homoeostasis and cardiac conduction, monocyte‐derived cells may promote destruction of the arterial wall and the myocardium, leading to organ ischaemia and heart failure. Influencing myeloid cell flux and phenotype shifts emerges as a therapeutic opportunity in many disease areas, including atherosclerosis, acute myocardial infarction, heart failure and stroke. However, it is currently unclear which cell subsets and drug targets are the most efficient and safest options. Here I review the neutrophil and macrophage supply chain and the cells’ emerging heterogeneity in the setting of atherosclerosis and ischaemic heart disease.