巨噬细胞移动抑制因子在动脉粥样硬化中的作用研究进展

动脉粥样硬化是动脉血管壁对损伤和刺激的慢性炎症和免疫反应，其发病机理尚未完全清楚。系列细胞因子对动脉粥样硬化的形成和发展等方面具有不同程度的作用，特别是巨噬细胞移动抑制因子和肿瘤坏死因子α在单核细胞聚集、粘附、迁移和巨噬细胞吞噬脂质等形成动脉粥样硬化过程中起着重要的作用。本文主要就巨噬细胞移动抑制因子在动脉粥样硬化进展中的变化和作用作一综述。     

Toll样受体4与动脉粥样硬化

动脉粥样硬化是一种慢性炎症疾病。Toll样受体家族(TLRs)识别抗原相关的分子模式(PAMPs)后激发先天性免疫反应。TLR4不仅识别外源性配体脂多糖(LPS),也识别动脉损伤过程中表达的内源性配体。越来越多的研究表明TLR4可能在动脉粥样硬化病变的发生和发展过程中发挥主要作用。现对近年有关TLR4在动脉粥样硬化中的作用的研究进展作一综述。此外,还将讨论对TLR4信号的可能干预措施。     

炎症反应在动脉粥样硬化发病学中的作用

动脉粥样硬化及其并发症是西方国家和日本最常见的死亡原因。在过去十年中,尽管出现了几种学说或假说,但没有一种能够完整地解释动脉粥样硬化发病机制的全过程,因为此疾病与多种危险因子有关。不仅如此,现在还有一种被普遍接受的观点认为动脉粥样硬化是一种特殊的慢性炎症过程,这种炎症过程源于血浆脂蛋白、细胞组分(单核/巨噬细胞、T淋巴细胞、内皮细胞和平滑肌细胞)与动脉壁细胞外基质间的相互作用。组织学观察发现,从动脉粥样硬化早期病变(脂纹)到复合病变具有慢性炎症的所有特征。现已证明,致动脉粥样硬化形成的脂蛋白,如氧化型低密度脂蛋     

MicroRNA调控动脉粥样硬化的研究新进展

正动脉粥样硬化(AS)是心血管系统的弥漫性病变,研究表明AS由动脉血管内皮损伤、脂蛋白渗入并沉积于动脉内膜下及触发动脉壁的慢性炎症所致,涉及血管壁的免疫和非免疫细胞成分参与的复杂过程。AS的并发症如心肌梗塞,脑血管意外和外周动脉疾病在世界范围内的发病率和死亡均较高。积累的研究揭示了微小核糖核酸(miRNA)是AS发生发展中的关键调节因子。本文主要就近年来MicroRNA在AS进展中的调控作用相关研究作一综述。     

PET/CT及其结合用示踪剂无创检测动脉粥样硬化性斑块和炎症的研究进展

<正>动脉粥样硬化是众多心脑血管疾病(冠心病、脑卒中、腹主动脉瘤和外周动脉疾病)发生、发展的直接原因。研究表明动脉粥样硬化本质上是一种慢性炎症增生性疾病〔1〕。在长期的促动脉粥样硬化危险因子(如吸烟、高血压、高脂血症、糖尿病以及高同型半胱氨酸血症等)的作用下,血管内皮受到损伤或功能异常,导致动脉粥样硬化的形成;动脉粥样硬化斑块主要由脂质、钙盐和炎症细胞构成〔2〕。随着动脉粥样硬化性疾病的     

关于炎症的新见解

正炎症是心脏病的主要病因,最近的研究再一次开始研究炎症动脉内出现了含有胆固醇的斑块(称为动脉粥样硬化)是大多数心脏病发作以及中风的根本原因。研究人员早就认识到慢性炎症会诱发这种动脉损伤过程(参见后文"了解炎症")。现在,他们正在努力寻找更好的方法来解决问题。治疗炎症至关重要,即使人们采取其他措施来降低心脏病的     

动脉壁脂蛋白受体与动脉粥样硬化

动脉粥样硬化的发生发展过程包括多个环节 ,如血管内皮损伤、脂质浸润、单核及淋巴细胞浸润、免疫反应、平滑肌细胞及细胞外基质增殖、血栓形成等。动脉粥样硬化斑块上表达有多种脂蛋白受体 ,其中大部分参与致动脉粥样硬化过程 ,它们不仅可介导细胞摄取脂蛋白 ,促进泡沫细胞的形成 ,还可能参与多种其它过程 ,如细胞粘附、免疫反应及细胞激活 ;亦有个别受体 ,如清道夫受体BI,参与抗动脉粥样硬化过程。本文对动脉粥样硬化斑块上表达的脂蛋白受体 ,包括清道夫受体家族成员、低密度脂蛋白受体家族成员及载脂蛋白B4 8受体 ,以及它们在动脉粥样硬化发生中的作用作一综述     

磷脂转运蛋白与脂蛋白代谢和动脉粥样硬化

动脉粥样硬化性心脑血管疾病是困扰人类健康的首要慢性炎症性疾病。而脂蛋白代谢异常是公认的动脉粥样硬化主要危险因素。2001年哥伦比亚大学的研究人员发现磷脂转运蛋白可以通过影响脂蛋白代谢进而改变动脉粥样硬化的易感性，从而开启了长达十多年的磷脂转运蛋白热点研究。　从动物实验到人群调查使得人们对磷脂转运蛋白在脂蛋白代谢和动脉粥样硬化中作用的认识不断深入。     

炎症与动脉粥样硬化

动脉粥样硬化(atherosclerosis,AS)发病机制的研究已经经历了一个多世纪,主要围绕4种学说:脂肪浸润学说、血小板聚集和血栓形成学说、平滑肌细胞克隆学说和损伤反应学说。近年来研究者发现,动脉粥样硬化的病理表现具有炎症病理的基本表现形式:变质、渗出和增生。其形成过程中也会出现类似类风湿性关节炎、慢性胰腺炎和肝硬化等慢性炎症性疾病的细胞间相互作用。随着炎症细胞和炎症介质的不断检出,动脉粥样硬化不再被认为是单纯的动脉壁脂质堆积的疾病,而是进展性炎症反应,符合炎症表现的普遍规律。因此,Ross教授在其损伤反应学说的基础上,…     

白介素10与动脉粥样硬化的研究现状

炎症在血管壁粥样硬化损害形成过程中起主要作用。脂质代谢、血管内皮损伤和炎症之间密切关联,动脉粥样硬化斑块的发生、发展与系统炎症密切相关,这些发现使抗炎细胞因子白介素10倍受关注。白介素10通过抑制多种促炎细胞因子的产生、下调细胞黏附分子的表达和抑制免疫反应等从从发挥抗动脉硬化作用。近几年,白介素10在抗动脉粥样硬化方面有新发现,在稳定性斑块与不稳定性斑块疾病血浆白介素10水平的临床研究结果不确定。因此,本文就白介素10在斑块内表达,抗动脉粥样硬化机制,白介素10基因多态性与动脉粥样硬化的关系以及白介素10血浆水平对动脉粥样斑块稳定性估计作一综述。     

Autoimmunity in atherosclerosis: a protective response losing control?

Atherosclerosis is a chronic inflammatory disease characterized by accumulation of oxidized lipoproteins, increased cell death and hypertrophic degeneration of the arterial intima. The disease process is associated with local formation of modified self antigens that are targeted by both innate and adaptive immune responses. Although it remains to be firmly established it is likely that these autoimmune responses initially have a beneficial effect facilitating the removal of potentially harmful rest products from oxidized LDL and dying cells. However, studies performed on hypercholesterolaemic mice deficient in different components of the immune system uniformly suggest that the net effect of immune activation is pro-atherogenic and that atherosclerosis, at least to some extent, should be regarded as an autoimmune disease. These observations point to the possibility of developing new treatments for atherosclerosis based on modulation of immune responses against plaque antigens, an approach presently tested clinically for several other chronic inflammatory diseases with autoimmune components. Pilot studies in animals have provided promising results for both parental and oral vaccines based on oxidized LDL antigens. The time when this concept is ready for clinical testing is rapidly approaching but it will be important not to underestimate the difficulties that will be encountered in transferring the promising results from experimental animals into humans.     

Regulatory T-cell immunity and its relevance to atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the arterial wall where both innate and adaptive immune responses contribute to disease initiation and progression. Recent studies from several groups suggest that subtypes of T cells, called regulatory T cells, previously shown to maintain immunological tolerance, inhibit the development and progression of atherosclerosis. Here, we review the current knowledge on the regulatory T-cell response and the major cytokines involved in its modulation in the context of atherosclerosis.     

The role of high-density lipoprotein in inflammation

High-density lipoprotein (HDL) appears to have evolved as part of the innate immune system, which in part uses an enhanced oxidative state as a nonspecific means of protecting against many pathogens. In the absence of acute or chronic inflammation, HDL is anti-inflammatory in mice, rabbits, and humans. However, with the onset of a systemic inflammatory state such as what occurs in atherosclerosis, HDL becomes pro-inflammatory, enhancing the inflammatory response. The major apolipoprotein of HDL is apoA-I, which may be altered by oxidative processes in patients with atherosclerosis. As a result, HDL from such patients is less efficient in promoting cellular cholesterol efflux. The ability of HDL to inhibit the inflammatory properties of oxidized phospholipids and low-density lipoproteins is also significantly altered. In mice and monkeys, the administration of an apoA-I-mimetic peptide renders pro-inflammatory HDL anti-inflammatory, improves HDL-mediated cellular cholesterol efflux; in mice, it dramatically inhibits atherosclerosis. Understanding the role of HDL in inflammation may lead to new diagnostic and therapeutic approaches to atherosclerosis and other inflammatory conditions.     

动脉粥样硬化的炎症应答特征及运用

动脉粥样硬化是多种心血管疾病的共同病理基础。越来越多证据表明,炎症在动脉粥样硬化的病理生理过程中发挥重要作用。动脉粥样硬化的发展受先天性免疫与适应性免疫细胞成分调控,且与全身炎症水平相关,多种炎症因子可作为动脉粥样硬化相关心血管疾病的预测指标。同时,一些抗炎治疗的临床试验表明,降低系统性炎症因子水平能够减少心血管事件风险。文章重点阐述了炎症在动脉粥样硬化中的作用、动脉粥样硬化发展中免疫应答的特征,以及目前针对动脉粥样硬化抗炎治疗的临床研究进展,以期为动脉粥样硬化治疗提供新的策略及靶点。     

Inflammatory reactions in the pathogenesis of atherosclerosis

Atherosclerosis and its complications constitute the most common causes of death in Western societies and Japan. Although several theories or hypotheses about atherogenesis have been proposed during the past decades, none can completely explain the whole process of the pathogenesis of atherosclerosis because this disease is associated with multiple risk factors. In spite of this, the concept that atherosclerosis is a specific form of chronic inflammatory process resulting from interactions between plasma lipoproteins, cellular components ( monocyte/macrophages, T lymphocytes, endothelial cells and smooth muscle cells ) and the extracellular matrix of the arterial wall, is now well accepted. Histologically, atherosclerotic lesions from the early-stage ( fatty streak ) to more complicated lesions possess all the features of chronic inflammation. It has been demonstrated that atherogenic lipoproteins such as oxidized low density lipoprotein ( LDL ), remnant lipoprotein (beta-VLDL) and lipoprotein [ Lp ] ( a ) play a critical role in the pro-inflammatory reaction, whereas high density lipoprotein ( HDL ), anti-atherogenic lipoproteins, exert anti-inflammatory functions. In cholesterol-fed animals, the earliest events in the arterial wall during atherogenesis are the adhesion of monocytes and lymphocytes to endothelial cells followed by the migration of these cells into the intima. It has been shown that these early events in atherosclerosis are triggered by the presence of high levels of atherogenic lipoproteins in the plasma and are mediated by inflammatory factors such as adhesion molecules and cytokines in the arterial wall. The development of genetically modified laboratory animals ( transgenic and knock-out mice and transgenic rabbits ) has provided a powerful approach for dissecting individual candidate genes and studying their cause-and-effect relationships in lesion formation and progression. The purpose of this article is to review the recent progress regarding the inflammatory processes during the development of atherosclerosis based on both human and experimental studies. In particular, we will address the mechanisms of atherogenic lipoproteins in terms of inflammatory reactions associated with hypercholesterolemia. Understanding the molecular mechanisms responsible for inflammatory reactions during atherogenesis may help us to develop novel therapeutic strategies to control, treat and prevent atherosclerosis in the future.     

Toll样受体与冠心病

冠心病是一种慢性炎症性免疫性疾病,冠心病的各种危险因素通过对Toll样受体家族基因和其下游炎症网络的调控,参与冠心病的炎症和免疫反应。炎症和免疫反应损伤血管,引起脂质浸润,平滑肌细胞增殖,导致斑块形成,炎症免疫反应又可以促进斑块的发展。Toll样受体介导冠状动脉粥样斑块的发生、进展、斑块不稳定乃至破裂等。干预Toll样受体家族,可能是冠状动脉粥样硬化性心脏病防治的新靶点。     

淋巴管:干预动脉粥样硬化发生发展的潜在途径

动脉粥样硬化是一种慢性炎症性疾病,是血管壁对各种损伤的异常反应。虽然影响动脉粥样硬化的因素很多,但淋巴管在动脉粥样硬化中的作用一直被忽视。传统上认为淋巴管是将间质液回流至血液循环的通道。在早期的研究中,发现动脉粥样硬化周围存在大量淋巴管,但两者之间的关系一直不清楚。近期研究发现淋巴管不仅参与动脉炎症的起始和消退,在胆固醇逆转运中也发挥着积极作用。此外,改善淋巴功能或促进局部淋巴管生成似乎可以减轻动脉粥样硬化的进展。因此,研究淋巴管与动脉粥样硬化的关系对干预动脉粥样硬化的发生发展具有重要意义。文章介绍了淋巴管与动脉粥样硬化发生发展相关的炎症、胆固醇逆转运以及免疫等因素的关系,以期为动脉粥样硬化干预策略的研究提供新的视角。     

Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis

Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti‐inflammatory therapies for this chronic disease.     

免疫细胞在动脉粥样硬化炎症进展中的双刃剑作用

炎症在动脉粥样硬化发展过程中起到十分重要的作用.动脉粥样硬化病理过程由动脉内皮损伤和血浆胆固醇水平异常引起,随后通过炎症反应招募各种免疫细胞进入动脉内膜参与斑块的形成与进展,这些细胞包括巨噬细胞、树突状细胞、平滑肌细胞、T细胞、B细胞和肥大细胞等.其中每一种免疫细胞又由促炎亚群和抗炎亚群共同组成,并产生相应的促炎因子与...     

Autoimmunity in atherosclerosis: lessons from experimental models

The modern view of atherosclerosis is of a chronic inflammatory disorder. In accord with this paradigm, the process of uninhibited influx of fat to the vessel wall results from an 'adequate' response to various forms of injury (i.e. turbulence, infections, modified lipoproteins). This idea has been further extended by several groups, to assume that the atherosclerotic lesion can be the target of an autoimmune mediated attack. According to this hypothesis, the site of initiation of the plaque should bear/express the target autoantigen, whereas concomitantly a respective immune response is generated in the periphery. The examples illuminating this notion are beta2GPI as a target autoantigen, HSP60/65 an oxidized-LDL. Herein we present evidence to support the involvement of autoimmune mechanisms in atherogenesis based on the experience from experimental models and human studies.