微小核糖核酸在心房颤动心房电重构中的作用

心房颤动是临床上最常见的快速型心律失常,致残、致死率高。心房颤动发病机制复杂,心房电重构是其中的中心环节之一。心房电重构导致心房有效不应期缩短、传导速度减慢,传导异质性增加,利于心房颤动的发生与维持。微小核糖核酸(miRNA)是一类内源性非编码小分子RNA,通过与靶基因mRNA的3'-非编码区(3-untranslated region,3'-UTR)结合,在转录后水平对靶基因的表达进行调节。近来的研究发现miRNA在心房颤动心房电重构中起着重要作用,本文将就这一问题展开阐述,为进一步理解心房颤动电重构的机制提供理论基础,为心房颤动的防治提供一些新的思路。     

MicroRNA-432与TGF-β1在风湿性心脏病合并心房颤动患者中的表达

正心房颤动(简称房颤)是临床上最为常见的心律失常,具有高致残率和高致死率特点~[1]。微小RNA(microRNA,miRNA)是新发现的一类高度保守的内源性非编码小RNA,是基因表达转录后调节的重要分子,能够通过与靶mRNA特异性的碱基配对引起靶mRNA的降解或者抑制其翻译,从而对基因进行转录后表达的调控~[2]。miRNA通过对编码心房肌电重构与结构重构基因调节,参与房颤的发生与维持。而房颤时发生心房结构重构机制可能包括:心房肌局部肾素-血管紧张素系统     

环状RNA在心房颤动发生中的作用及应用

近年来研究表明，环状RNA在心房组织中的异常表达与心房颤动(简称房颤)结构重构和电重构密切相关。环状RNA与微小RNA相互作用靶向参与调控不同离子通道基因和纤维化相关基因的表达，这为房颤发病的分子机制理解提供了一个新的方向，同时也为未来房颤的诊疗提供了新的诊断标志物和治疗靶点。     

与心房重构相关microRNAs的研究进展

小分子非编码RNA（microRNA或miRNA）被发现在动、植物体内发挥着广泛而重要的调控作用。近来又有研究发现microRNAs与机体心房纤颤（房颤）相关,但具体发病机制尚不清楚。旁颤发生的病理生理机制非常复杂,包括钙离子稳态失调、离子通道改变、心房电生理及结构重构等,研究发现microRNAs参与了心房电重构及结构重构,本文对目前研究中涉及心房重构的一些microRNA及其作用进行了综述,现报告如下。     

microRNA:心房颤动中心房重构的调控者

microRNA是一类内源性非编码小RNA,可参与生物过程中转录后水平基因表达的调控。近年来,有关于microRNA在心房颤动(简称房颤)中心房组织重构与电重构的调控作用有了新的认识。已有研究表明miR-21、miR-29、miR-133、miR-30、miR-590等可参与房颤过程中心房间质纤维化的调控,而miR-1、miR-26、miR-328、miR-499等被发现与房颤过程中内向整流钾通道、L型钙通道,小电导钙激活钾通道等多种离子通道重构有关。这些研究深化了我们对房颤中心房重构的分子调控机制的认识,为房颤机制的研究与防治提供了新的前景。诚然,对于房颤中microRNA的确切调控机制以及基于microRNA的干预治疗措施的有效性、安全性仍需进一步的研究论证。     

永久性心房颤动患者心房组织相关微小核糖核酸调控网络研究

目的:寻找永久性心房颤动(p AF)发病相关的关键微小核糖核酸(miRNA)及其调控靶基因。方法:表达谱芯片比较pAF患者(n=7)和窦性心律健康成人(n=4)的左心房组织的转录组,miRNA芯片筛选pAF相关差异表达miRNA,进行靶基因预测,与表达谱芯片的筛选结果进行负相关分析后的基因集合进行显著性功能分析(GO-Analysis),得到显著性、低误判率、靶向性的功能以及对应的靶基因;利用miRNA与靶基因之间的靶向调控关系,构建差异miRNA与分析后得到的显著性GO所属交集靶基因的调控网络(miRNA-Gene-Network),得到网络中起核心调控作用的miRNA和被miRNA调控的关键靶基因;采用qRT-PCR方法检验另一组pAF患者(n=5)和窦性心律健康成人(n=4)的左心房组织标本,验证所寻找的miRNA和被调控的关键靶基因。结果:26个差异表达的miRNA(16个上调、10个下调)和610个靶基因有显著性改变(fold change2,P0.05),与miRNAs芯片预测靶基因负相关后建立miRNA-靶基因调节网络发现与pAF显著相关的20个miRNA和107个靶基因,相关度最高的是miR-144、miR-1284、miR-1827、miR-1、miR-3613-3p及miR-101;其调控的重要靶基因包括PTEN、TAOK1、RUNX1及TPM3等,参与心房电生理改变、成纤维细胞及胎儿基因表达等心房重构机制。qRT-PCR验证结果提示,这些主要的miRNA和靶基因与pAF发生密切相关。结论:通过表达谱基因芯片与miRNA芯片联合分析pAF左心房组织标本,构建miRNA-靶基因调控网络,是发现pAF相关关键miRNA及其调控靶基因一种方法。     

MicroRNA-21调控心脏结构重构的研究进展

心脏结构重构是心脏应对压力负荷、维持心脏正常输出的适应性反应,最终导致心脏组织硬化、功能失调,是心血管疾病发展的关键过程,可见于心肌梗死、心力衰竭、心房颤动及主动脉狭窄等心脏性疾病。MicroRNA-21(miR-21)是新近发现的与心脏结构重构密切相关的小分子RNA。临床和动物模型的最新研究结果表明,miR-21通过调控相关靶基因的表达,介导相关信号通路,参与心脏结构重构发生和发展,并可能成为诊断心脏结构重构的生物标志物和治疗靶点。     

microRNA在心房颤动电重构及治疗中的进展

正心房颤动(房颤,AF),是临床上最常见的心律失常之一,房颤具有极高的卒中、心力衰竭风险,也是认知障碍、痴呆的独立危险因素。房颤主要由心房重构,自主神经系统改变,炎症因子和氧化应激,肾素-血管紧张素-醛固酮系统异常等引起~([1])。而心房重构在房颤中起到至关重要的作用。miRNA是一类大约22个核苷酸的内源性非编码小分子RNA,通过与靶mRNA结合,参与mRNA降解或转录后翻译抑制,调控靶基因的表达。近年来大量研究表明,miRNA     

心房颤动致心房重构分子机制研究进展

心房颤动是临床上一种常见的心律失常,心房颤动致心房重构是近年来研究发现的一个重要的电生理现象。心房颤动本身能够导致心房电生理、功能和结构的改变。本文综述了心房颤动致心房快速的电生理变化和缓慢的蛋白质表达及其分子改变机制。通过对心房电生理重构、离子重构和蛋白质重构和超微结构及其功能变化等不同方面的全面阐述,探讨了心房重构的分子机制研究进展。防治心房颤动新的策略将取决于心房重构机制更好的理解。     

MicroRNA-1的心律失常调控作用

微小RNA（miRNA）是近年来新发现的一类小分子非编码RNA,其通过调节靶基因mRNA的稳定性或抑制翻译过程而发挥作用。miR-1在人类心脏中表达最为丰富,与心律失常的发生关系密切,有大量文献报道可通过调节其表达而上调或下调多种心脏电活动相关离子通道或蛋白水平来调控心律失常。本文就miR-1调控心律失常的作用机制作一综述。     

Atrial remodeling in atrial fibrillation and some related microRNAs

Atrial fibrillation is the most common sustained arrhythmia associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. The role of atrial remodeling has emerged as the new pathophysiological mechanism of atrial fibrillation. Electrical remodeling and structural remodeling will increase the probability of generating multiple atrial wavelets by enabling rapid atrial activation and dispersion of refractoriness. MicroRNAs (miRNAs) are small non-coding RNAs of 20-25 nucleotides in length that regulate expression of target genes through sequence-specific hybridization to the 3' untranslated region of messenger RNAs and either block translation or direct degradation of their target messenger RNA. They have also been implicated in a variety of pathological conditions, such as arrhythmogenesis and atrial fibrillation. Target genes of miRNAs have the potential to affect atrial fibrillation vulnerability.     

MicroRNA与心房颤动关系的研究进展

心房颤动是最常见的持续性心律失常,并有较高的发病率和死亡率。其流行率预计在未来几年会进一步增加。尽管在过去十年中出现了心房颤动病理生理学的新分子概念,但目前可用的治疗方法仍存在主要局限性,包括效果差和严重的副作用,如心室恶性心律失常等。心房电重构、结构重构和自主神经重构是心房颤动的发病基础,但驱动这种重构的确切机制仍不完全清楚。MicroRNA代表大量小非编码RNA的亚组,降解或抑制其靶m RNA的翻译,从而调节基因表达并在广泛的生物学过程中起重要作用。临床上,越来越多的证据表明micro RNA在心血管疾病的发生发展中发挥关键作用。     

炎症反应与心房颤动的研究进展

心房颤动（房颤）是临床上最常见的心律失常,常与心血管系统不良事件相关。房颤的核心机制是心房重构,包括电重构、结构重构和自主神经重构。炎症是机体应对损伤的一种修复反应,过度的炎症反应常导致各种疾病的发生。随着对房颤的深入研究,炎症反应在房颤发生、发展过程中的作用被广泛关注。炎症标志物可预测或诱发房颤,反之,房颤本身也可促进炎症反应的进一步发展。研究炎症反应标志物和开发新的抗炎药物将为房颤的诊治提供新的思路。     

心率与心房颤动关系的研究进展

心房颤动（简称“房颤”）是临床上最常见的心律失常,其发病率随年龄增长而增加。心房重构是房颤的核心机制,包括电重构、结构重构及自主神经重构。自主神经功能障碍在房颤的发生、发展中起着重要的作用,而心率可以间接反映自主神经功能。心率与房颤发生的关系以及房颤射频消融术后心率变化与房颤复发关系复杂,且一直在研究中。     

心房有效不应期离散度与心房颤动

心房颤动是临床最常见的心律失常之一,有较高的致残率及致死率,关于心房颤动的机制有较多的学说,目前研究已经证实心房电重构能够促进心房颤动的发生与维持,心房电重构包括心房有效不应期的缩短,心房有效不应期离散度的增加及局部电传导的减慢,现就心房有效不应期离散度与心房颤动的关系及其影响机制做一综述。     

Mechanisms of atrial remodeling and clinical relevance

PURPOSE OF REVIEW: Atrial fibrillation usually occurs in the context of an atrial substrate produced by alterations in atrial tissue properties referred to as remodeling. Remodeling can result from cardiac disease, cardiac arrhythmias, or biologic processes such as senescence. Recent advances in understanding remodeling have allowed for insights into mechanisms underlying atrial fibrillation that have been transferred from experimental models to humans. This paper reviews recent progress in understanding atrial remodeling, as well as the consequent clinical insights into atrial fibrillation pathophysiology and treatment. RECENT FINDINGS: Two principal forms of remodeling have been described in animal models of atrial fibrillation: ionic remodeling, which affects cellular electrical properties, and structural remodeling, which alters atrial tissue architecture. Atrial tachycardias (particularly rapid tachyarrhythmias such as atrial flutter and atrial fibrillation) cause ionic remodeling, which decreases the atrial refractory period and promotes atrial reentry. Congestive heart failure produces atrial interstitial fibrosis, which promotes arrhythmogenesis by interfering with atrial conduction properties. Recent animal studies have provided insights into the pathways involved in remodeling, and have indicated the pathophysiological role of remodeling in specific contexts. In addition, work in animal models has provided information about pharmacological interventions that can prevent the development of remodeling. Clinical studies have shown that novel approaches to remodeling prevention identified in animal work have potential therapeutic value in man. SUMMARY: Understanding atrial remodeling has the potential to improve our appreciation of the pathophysiology of clinical atrial fibrillation and to allow for the development of useful new therapeutic approaches.     

醛固酮受体拮抗剂治疗心房颤动的研究进展

心房颤动是临床上最常见的持续性心律失常,近年来研究表明心房重构是心房颤动发生和维持的中心环节,心房重构包括电重构和结构重构,然而心房重构确切的机制尚未完全明确。近年来的研究表明,醛固酮与心房重构有着密切的关系。文章综述了醛固酮影响心房重构的机制以及醛固酮受体拮抗剂治疗心房重构的研究。     

Novel pharmacological therapies for atrial fibrillation

PURPOSE OF REVIEW: Atrial fibrillation is a common yet difficult cardiac rhythm to treat. Limitations of the currently available medications, increasing complexity of atrial fibrillation patient populations and the prevalence of the condition have made new drug development crucial. Our understanding of the pathophysiology of atrial fibrillation has increased tremendously over the years. The importance of electrical remodeling and structural remodeling has been widely appreciated and has opened new avenues for pharmacological research. RECENT FINDINGS: Novel ion channel blockers have targeted atrial-specific ion channels or a combination of ion channels in order to maximize efficacy and minimize proarrhythmic risk. Understanding of atrial fibrillation as a metabolically complex condition with activation of multiple signaling cascades has fuelled drug development in a new direction. Exciting new drugs inhibiting fibrosis, cellular hypertrophy and improving cell-cell communication may help treat chronic atrial fibrillation in the future. SUMMARY: Continuing progress in our knowledge of the ionic and structural remodeling in atrial fibrillation will only accelerate the search for a safe antidote. In the future focal pharmacological modulation may help target specific targets in diverse populations. The potential of many of these pharmacotherapies, however, will need to be tested in large randomized trials before our faith in them is realized.     

Electrical and structural remodeling: role in the genesis and maintenance of atrial fibrillation

Atrial fibrillation (AF) and congestive heart failure (CHF) are 2 frequently encountered conditions in clinical practice. Both lead to changes in atrial function and structure, an array of processes known as atrial remodeling. This review provides an overview of ionic, electrical, contractile, neurohumoral, and structural atrial changes responsible for initiation and maintenance of AF. In the last decade, many studies have evaluated atrial remodeling due to AF or CHF. Both conditions often coexist, which makes it difficult to distinguish the contribution of each. Because of atrial stretch in the setting of hypertension or CHF, atrial remodeling frequently occurs long before AF arises. Alternatively, AF may lead to electrical remodeling, that is, shortening of refractoriness due to the high atrial rate itself. In many experimental AF or rapid atrial pacing studies, the ventricular rate was uncontrolled. In those studies, atrial stretch due to CHF may have interfered with the high atrial rate to produce a mixed type of electrical and structural remodeling. Other studies have dissected the individual role of AF or atrial tachycardia from the role CHF plays in atrial remodeling. Atrial fibrillation itself does not lead to structural remodeling, whereas this is frequently produced by hypertension or CHF, even in the absence of AF. Primary and secondary prevention programs should tailor treatment to the various types of remodeling.     

转化生长因子-β1对心房结构重构及细胞骨架蛋白的影响

心房颤动是临床上最常见的持续性心律失常。大量研究发现,心房颤动的发生发展与心房结构重构密切相关,而心房纤维化是最主要的结构重构改变。转化生长因子-β1是心房颤动纤维化重构中重要的致纤维化因子,不仅能引起细胞间质重构,还能影响心肌细胞骨架重塑及相关骨架蛋白表达异常。特别是使心脏特异性肌动蛋白交联蛋白α-actinin-2表达增加。细胞骨架蛋白参与了结构重构改变。现对转化生长因子-β1对心房结构重构及心房肌细胞骨架蛋白的影响进行综述。