关注免疫炎症及其标志物在动脉硬化性心血管病中的作用

正免疫是机体抵抗外敌感染和入侵的自我保护行为,适当的免疫反应能清除病原体,有利于机体,但免疫反应过度则对机体产生伤害,炎症反应就是剧烈的免疫反应的结果。随着研究的不断深入,炎症与动脉粥样硬化(arteriosclerosis,As)的关系已成为近年的研究热点。大量研究证实,炎症就是免疫的过程,免疫细胞中单核/巨噬细胞、肥大细胞、自然杀伤细胞、中性粒细胞和树突状细胞,广泛参与As过程。As是由脂蛋白、高血压、高血糖、自由基、感染性微生物、吸     

Toll样受体4与动脉粥样硬化

炎症免疫反应是机体对微生物侵袭的天然防御反应，免疫细胞通过其细胞膜上的受体识别外来微生物的配体。从而启动宿主的炎症免疫反应。研究表明，动脉粥样硬化（atherosclerosis，As）是一种慢性炎症疾病，伴有免疫反应的炎症过程在As的发生和发展中起着决定性作用。但免疫反应在其中的分子生物学机制至今还未阐明。最近发现的Toll样受体（toll-like receptors，TLRs）是模式识别受体，能调节先天与获得性免疫，在抗微生物感染和识别内源性配体中起重要作用。TLRs识别内外源性配体后，启动炎性应答通路，诱导炎性因子大量产生，从而对机体组织产生保护和损伤作用。大量证据表明，TLRs在As中起着重要作用。本文就TLR4与As的相关研究作一综述。     

免疫细胞亚群平衡在动脉粥样硬化中的机制与中医药调节作用的研究进展

动脉粥样硬化(As)是由调控促炎与抗炎平衡的免疫细胞及细胞因子等共同参与的慢性炎症性疾病,适应性免疫细胞在其中发挥重要作用。中医药因多途径、多靶点的优势疗效广泛应用于防治As。本文就As炎症反应中适应性免疫系统不同细胞亚群协同发挥促炎、抗炎的作用机制及中医药调节免疫平衡对As的影响作一综述。     

组胺与固有免疫调控及其在心血管疾病中的作用

组胺是人体内重要的参与免疫调节和过敏反应、神经信号传递、胃酸分泌、造血细胞生成等生理病理过程的小分子生物胺。组胺通过作用于细胞表面的组胺受体,激活相应的胞内信号通路,进而发挥一系列生理效应。已有研究表明,炎症与免疫反应贯穿冠心病、心力衰竭、心肌心包炎等心血管疾病的发生发展过程,其中组胺的作用颇受关注。本综述将着眼于探讨组胺对固有免疫反应的调控作用及其对心血管疾病的影响。     

Siglec家族与动脉粥样硬化相关性免疫细胞关系的研究进展

动脉粥样硬化(As)是一种慢性炎症性血管疾病,各类免疫细胞的活性在其形成过程中均具有重要的作用。研究证实唾液酸结合性免疫球蛋白样凝集素(Siglec)家族与多种炎症免疫细胞的活性调节关系密切,如Siglec-1,5和7与单核/巨噬细胞活性显著相关,Siglec-2,10参与B淋巴细胞活性调节,Siglec-5,9和14能够调控中性粒细胞活性等,提示Siglec家族可能通过调节免疫细胞活性参与As形成的过程。尽管目前尚缺乏全面的直接证据,但已证实Siglec-1与As病变的形成显著相关,且抑制其表达能够显著减轻病变的程度。为从糖生物学的角度审视As形成中炎症免疫因素的作用机制,并探索防治As的可能新靶点,本文拟对Siglec家族与As相关性免疫细胞关系的研究进展作一综述。     

中性粒细胞HDC/histamine信号:抗血栓治疗的新靶点

血栓及其并发症是一种危害健康的临床病症。中性粒细胞胞外诱捕网(NET)是由中性粒细胞释放、解聚的染色质形成的细胞外的纤维网络,通过激活血小板、加速凝血从而促进血栓形成影响疾病转归。组氨酸脱羧酶(HDC)是催化组胺(histamine)生成的关键酶,在中性粒细胞,尤其是骨髓内不成熟CD11b⁺髓系细胞内有高水平表达。组胺信号参与过敏反应、胃酸分泌、炎症、免疫反应和肿瘤发生等多种生理和病理生理事件。组胺及其下游相关信号对中性粒细胞极化、NET形成和血栓发生发展的调控,可能成为血栓性疾病靶向药物研发的重要参考。文章主要对表达HDC的中性粒细胞在血栓形成和发生发展的作用进行综述。     

Toll样受体4在幽门螺旋杆菌感染致动脉粥样硬化中的作用

动脉粥样硬化(As)是一种慢性炎症反应性疾病,幽门螺旋杆菌(Hp)感染与As性疾病的相关性研究日益引起关注,其促进As进展的具体机制尚未完全阐明。Toll样受体4(TLR4)是天然免疫反应的重要受体,在微生物致病因子及其产物引起宿主主动和被动免疫中有重要作用,参与动脉硬化的发生和发展。TLR4在As形成的多种细胞均有表达。TLR4通过捕获Hp的致病因子脂多糖后启动细胞内信号途径,进而引起核因子κB依赖的转录,引起一系列细胞因子及化学因子的释放,增强炎症反应而致病。本文就Hp、TLR4信号通路及其在As中的作用作一综述,为As疾病的防治提供新思路。     

NK细胞与冠心病的关系

冠心病（CHD）是动脉粥样硬化导致器官病变的最常见类型,也是危害人类健康的常见病,近年来研究表明炎症免疫反应与CHD的发生、发展及心梗后的损伤修复密切相关。NK细胞作为先天性免疫系统的重要组成成分,参与了CHD的发生、发展及缺血后的心肌重塑。本文简要概括了NK细胞与CHD的研究进展,以期为CHD的治疗提供新的思路。     

NF-κB在肺部炎症性疾病中的作用

转录因子核因子—κB是一种调控基因表达的结合蛋白。它通过调控肺部炎症、免疫细胞和气道上皮细胞中许多重要的细胞因子、粘附分子的基因表达，而参与肺部的炎症、免疫反应，在肺部炎症性疾病中发挥着重要的作用，成为近年来研究的热点。     

动脉粥样硬化与免疫反应

动脉粥样硬化(atherosclerosis，As)斑块的形成是多因素导致的慢性炎症过程。多种致病因素可诱导血管壁局部发生炎性级联反应，导致临床表现的差异。同其它急性或慢性感染疾病一样，免疫反应参与As形成过程。     

巨噬细胞与间充质干细胞相互作用及其对缺血性心脏病的影响

心肌梗死发生后,缺血及周边区域发生的炎症反应贯穿了心肌组织修复及纤维化的始终。巨噬细胞作为炎症反应的重要组分,在心肌损伤后的修复过程中至关重要。不同亚型的巨噬细胞参与了心肌梗死的各个阶段,并发挥着吞噬凋亡细胞、促进血管新生、促进瘢痕形成等多种作用。移植间充质干细胞也因具有免疫调控、旁分泌心肌保护等多种效应,被广泛用于缺血性心衰的研究中。近年来研究发现,巨噬细胞和间充质干细胞在治疗缺血性心脏病中有着密切联系,间充质干细胞可减少促炎型巨噬细胞在炎症部位的募集,并诱导巨噬细胞由促炎型向抗炎型转化,从而促进心肌修复。而巨噬细胞可影响间充质干细胞的生存、增殖、迁移及免疫调控等功能,从而改变其心肌修复效果。本文就巨噬细胞与间充质干细胞相互影响及其在缺血性心脏病中的作用与应用前景进行综述。     

Ischemia/reperfusion injury: The role of immune cells

Ischemia/reperfusion (I/R) injury is an inflammatory condition that is characterized by innate immunity and an adaptive immune response. This review is focused on the acute inflammatory response in I/R injury, and also the adaptive immunological mechanisms in chronic ischemic disease that lead to increased vulnerability during acute events, in relation to the cell types that have been shown to mediate innate immunity to an adaptive immune response in I/R, specifically myocardial infarction. Novel aspects are also highlighted in respect to the mechanisms within the cardiovascular system and cardiovascular risk factors that may be involved in the inflammatory response accompanying myocardial infarction. Experimental myocardial I/R has suggested that immune cells may mediate reperfusion injury. Specifically, monocytes, macrophages, T-cells, mast cells, platelets and endothelial cells are discussed with reference to the complement cascade, toll-like receptors, cytokines, oxidative stress, renin-angiotensin system, and in reference to the microvascular system in the signaling mechanisms of I/R. Finally, the findings of the data summarized in this review are most important for possible translation into clinical cardiology practice and possible avenues for drug development.     

Communication in the Heart: the Role of the Innate Immune System in Coordinating Cellular Responses to Ischemic Injury

Ischemic cardiac injury is the leading cause of heart failure and mortality in the USA and is a major expense to health-care systems. Once the heart is injured, a highly dynamic and coordinated immune response is initiated, which is dependent on both resident and recruited leukocytes. The goal of the inflammatory response is to remove ischemic and necrotic material and to promote infarct healing. If this system is perturbed, the myocardium heals poorly, leading to significant left ventricular dysfunction. Understanding how inflammatory cells coordinate and interact with each other is required prior to designing therapeutic interventions that target pathological processes at play and leave untouched those processes that are protective. This review will discuss the intercellular cross talk between cells of the innate immune system following myocardial ischemic injury and how that response is coordinated over time.     

Role of adult bone marrow stem cells in the repair of ischemic myocardium: current state of the art

OBJECTIVE: To review the milestones in stem cell therapy for ischemic heart disease from early basic science to large clinical studies and new therapeutic approaches. MATERIALS AND METHODS: Basic research and clinical trials (systematic review) were used. The heart has the ability to regenerate through activation of resident cardiac stem cells or through recruitment of a stem cell population from other tissues, such as bone marrow. Although the underlying mechanism is yet to be made clear, numerous studies in animals have documented that transplantation of bone marrow-derived stem cells or circulating progenitor cells following acute myocardial infarction and ischemic cardiomyopathy is associated with a reduction in infarct scar size and improvements in left ventricular function and myocardial perfusion. RESULTS: Cell-based cardiac therapy has expanded considerably in recent years and is on its way to becoming an established cardiovascular therapy for patients with ischemic heart disease. There have been recent insights into the understanding of mechanisms involved in the mobilization and homing of the imported cells, as well as into the paracrine effect, growth factors, and bioactive molecules. Additional information has been obtained regarding new stem cell sources, cell-based gene therapy, cell-enhancement strategies, and tissue engineering, all of which should enhance the efficacy of human cardiac stem cell therapy. CONCLUSIONS: The recently published trials using bone marrow-origin stem cells in cardiac repair reported a modest but significant benefit from this therapy. Further clinical research should aim to optimize the cell types utilized and their delivery mode, and pinpoint optimal time of cell transplantation.     

Comparison of the natural history of new onset and exacerbated chronic ischemic heart disease. The Chest Pain Study Group

To compare the natural history of patients with new onset ischemic heart disease with that of patients with exacerbations of chronic ischemic heart disease, short- and long-term outcomes of 3,465 emergency room patients with acute ischemic heart disease at four community and three university hospitals were evaluated. Acute myocardial infarction was diagnosed in 598 (33%) of the 1,835 patients with a prior history of infarction or angina and 934 (57%) of the 1,630 without such a history (p less than 0.001). Patients with new onset ischemic heart disease with acute myocardial infarction were more likely than patients with infarction and exacerbated chronic ischemic heart disease to have Q wave infarction (57% versus 36%) and to receive thrombolytic therapy (11% versus 5%); they also had higher maximal creatine kinase levels (1,088 +/- 1,299 versus 733 +/- 906 U/liter) (p less than 0.0001 for all three). After adjustment for differences in clinical presentation and initial triage, patients with new onset ischemic heart disease with acute myocardial infarction were less likely than the comparison group to have congestive complications (odds ratio 0.63, 95% confidence interval 0.47 to 0.84, p less than 0.01) but not less likely to have arrhythmic, ischemic or overall complications. Among patients with angina without acute myocardial infarction, patients with new onset ischemic heart disease were less likely to have recurrent ischemic pain and congestive heart failure. In multivariate analysis of long-term follow-up data on 457 patients from one hospital, patients with new onset ischemic heart disease had better cardiovascular survival rates.(ABSTRACT TRUNCATED AT 250 WORDS)     

中叶素在糖尿病合并冠心病中的作用

中叶素(IMD)是近年来发现的一种新的心血管调节肽,是降钙素基因相关肽(CGRP)超家族新成员。既往研究发现,中叶素在缺血再灌注中具有重要的保护作用。流行病学和临床研究显示,糖尿病人群缺血性心脏病(心绞痛、心肌梗死)、充血性心力衰竭及粥样硬化性病变所致疾病的发生率及其严重程度远高于非糖尿病人群。因此,中叶素是否在糖尿病合并冠心病患者中具有保护作用有待探讨。文章就中叶素的生物学特性以及在糖尿病合并冠心病中的作用从基础研究到临床研究进展做一综述。     

Stem Cell Therapy: Pieces of the Puzzle

Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals.     

心肌缺血再灌注损伤机制研究的回顾与展望

心肌梗死是全球冠心病患者死亡的主要原因之一。在急性心肌梗死早期行经皮冠状动脉介入术、冠状动脉旁路移植术、药物等治疗手段,可恢复缺血区心肌组织血供,挽救濒死的心肌,降低患者的致死率。然而,心肌血供中断后,一定时间内再通恢复血供后,原缺血心肌可发生较缺血时更为严重的损伤,这一现象称为心肌缺血再灌注损伤(MIRI),其发生机制尚未完全阐明。文章就近年来MIRI机制的研究进展作一综述,阐述MIRI的病理生理机制,将有助于开发新的治疗干预手段,为临床治疗心肌梗死提供帮助。     

The Pathobiology of Acute Coronary Syndromes: Clinical Implications and Central Role of the Mitochondria

Ongoing investigation has provided new insights into the pathobiology of myocardial ischemic injury. These include an improved understanding of the roles of the major modes of cell injury and death, including oncosis, apoptosis, and unregulated autophagy, as well as the central role of the mitochondria in the progression of myocardial ischemic injury, reperfusion injury, and myocardial conditioning. This understanding is providing insights for developing new pathophysiologic, pharmacologic, and cell-based therapies, alone or in combination with percutaneous coronary interventions, for better preservation of myocardium and reduction of morbidity and mortality rates from ischemic heart disease.Key words: Apoptosis, autophagy, cardioprotection, inflammation mediators, ischemic preconditioning, myocardial, myocardial ischemia/physiopathology, myocardial reperfusion injury/physiopathology, myocardial stunning/physiopathology, myocytes, cardiac/pathology, mitochondria, myocardial reperfusion injury, myocardium/cytology/ultrastructure, myocytes, cardiac/pathology, necrosis/prevention & control, oncosis, regeneration/physiology, reperfusion injury, signal transduction, stem cell transplantationThe dynamic alterations in cells, tissues, and organs involving molecular, biochemical, structural, and functional changes constitute collectively the pathobiology of disease. The first purpose of this review is to relate fundamental knowledge of the pathobiology of acute coronary syndromes (ACS) to clinical manifestations and the clinical course of these conditions. The second purpose is to link this knowledge to opportunities for therapeutic interventions to favorably alter the clinical course and outcomes of ACS.