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。     

心房重构研究进展

心房重构是心房颤动（房颤）发生和维持的重要因素,包括电重构和结构重构。近年来心房重构机制研究逐渐深入,针对心房重构的房颤上游治疗成为研究热点。该文针对心房重构机制的研究进展和相关治疗作一综述。     

转录激活因子ELK-1在持续性心房颤动患者心房肌中表达下调

心房颤动（房颤）是临床上最常见的心律紊乱之一，其发病机制尚不甚清楚。目前证实，心房肌的电生理重构和结构重构是房颤发生、发展的基础。最近发现，心房肌在房颤状态下的重构是适应性的逆向分化。转录激活因子ETS样蛋白1（ETS-1ike1，ELK-1）作为ETS家族（命名缘于禽类白血病病毒基因E26）成员之一，在细胞分化调节中起着重要作用。因此推测，转录激活因子ELK-1参与调控房颤心房肌的分子和结构重构。本实验采用Western blot和免疫组化技术，观察了转录激活因子ELK-1在房颤心房肌的表达改变，以验证假设是否成立。     

心房颤动的研究现状及展望

<正> 近十年来,心房颤动(房颤)的研究取得了快速进展,无论机制、治疗方面,还是基因研究,都有了长足的进步,这主要体现在以下几个方面。1 对房颤的发病机制有了深入了解首先,众多学者对心房结构重构、电重构进行了多层次的研究,明确了心房重构是房颤发生的重要原因。结构重构主要表现为心房肌细胞超微结构的改变和心肌间质纤维化、胶原纤维重分布,导致局部心肌电活动传导异常,使激动传导减慢、路径曲折,从而促进房颤的发生和维持;电重构是指心房各部位由于离子通道重     

氧化应激在心房颤动发生维持中的作用

心房颤动（房颤）是临床上最常见的慢性心律失常。房颤使心房发生电重构及结构重构,然而心房重构发生的同时也加重房颤的发生及维持。有多项研究证实,氧化应激产物如活性氧能够影响房颤时心房电重构及结构重构,而房颤本身又使心房肌的氧化应激产物增加。房颤时心房氧化应激作用的机制可能与离子通道功能失调、NADPH氧化酶途径及线粒体损伤等有关。在一些近期的研究中也发现具有抗氧化作用的药物如他汀类、肾素-血管紧张素-醛固酮系统阻断剂可能通过防止心房重构,减少房颤发生。     

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     

心房颤动发病机制的相关研究进展

心房颤动（atrial fibrillation,AF）是老年人群中最为常见的心律失常,研究表明其发病机制与衰老、遗传突变、炎症反应、氧化应激、钙稳态异常、代谢异常等有关,越来越多的证据表明上述机制在心房电重构和结构重塑的演变中起着重要作用。在这篇综述中,我们讨论了房颤发生发展可能的分子机制,其中涉及多个典型的炎症途径,以及抗炎治疗、纠正代谢异常等方法 对房颤的防治潜力。     

L-型钙电流与心房电生理重构的研究进展

心房颤动的发生机制目前仍未清楚。心房电重构理论的提出为研完房颤的发生开辟了一个新领城。本文就近年来对心房快速除板所致的心房肌电生理重构、L-型钙电流的改变。L-型钙通道的分子重构。细胞内Ca^2 超负荷以及它们在房颤发生、发展和维持中的作用的研完进展予以综述。     

心房重构研究进展

心房重构是心房颤动(房颤)发生和维持的重要因素,包括电重构和结构重构。近年来心房重构机制研究逐渐深入,针对心房重构的房颤上游治疗成为研究热点。该文针对心房重构机制的研究进展和相关治疗作一综述。     

内皮素1及其受体基因表达与心房颤动的相关性研究

目的检测内皮素-1（ET-1）及其受体（ET—A和ET—B）mRNA在心房颤动（房颤）患者心房组织中的表达,探讨房颤患者心房电重构的分子机制。方法25例行心脏手术的患者分为3组,其中窦性心律组10例,持续性房颤组10例,阵发性房颤5例,于手术中获取右心耳组织,采用实时荧光定量聚合酶链式反应（FQ—PCR）方法检测ET-1前体（Pro—ET-1）、ET—A、ET—B的mRNA表达。结果（1）与窦性心律组相比,Pro-ET-1的mRNA水平在阵发性房颤组、持续性房颤组心房组织中均明显增加（P〈0．05）,持续性房颤组较阵发性房颤组亦明显增加（P〈0．05）。（2）与窦性心律组相比,ET—A和ET—B的mRNA水平在阵发性房颤组、持续性房颤组心房组织中明显降低（P〈0．05）,持续性房颤组较阵发性房颤组亦明显降低（P〈0．05）。结论房颤患者心房组织中内皮系统基因表达的变化可能是影响心房重构的分子机制之一,与房颤的发生和维持有关。     

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。     

Molecular mechanisms of remodeling in human atrial fibrillation

An important acknowledgement of the last several years is that atrial fibrillation (AF) modifies the electrical properties of the atrium in a way that promotes its occurrence and maintenance. This arrhythmogenic electrophysiological remodeling is well established, but can not explain by itself that 'AF begets AF'. This review describes molecular changes involving rapid functional alterations and slower changes in protein expression that cause electrical remodeling and contractile dysfunction in AF. An important molecular feature of AF is the reduction in L-type Ca(2+) channel function and protein expression. This reduction may serve to protect the cell against a potentially lethal Ca(2+) overload resulting from the increased activation rate in AF. Further, the review discusses the possible role of proteolytic systems, notably the calpains, as a mechanism linking Ca(2+) overload to reduced protein expression. Thus, it appears that the elaborate molecular changes in AF are directed primarily at protecting the myocyte from cellular stress. However, such early protection occurs at the expense of electrophysiological changes that promote the long-term maintenance of AF.     

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.     

Atrial electrophysiological remodeling caused by rapid atrial activation: underlying mechanisms and clinical relevance to atrial fibrillation.

One of the most exciting developments in our understanding of atrial fibrillation (AF) over the last several years has been the recognition that AF itself modifies atrial electrical properties in a way that promotes the occurrence and maintenance of the arrhythmia, a process termed 'atrial remodeling'. The principle stimulus for AF-induced atrial remodeling is the rapid atrial rate that results: rapid regular atrial pacing produces changes similar to those caused by AF in animal models. The mechanisms of atrial tachycardia-induced remodeling have been extensively explored, and involve changes in atrial electrophysiology associated with altered ion channel function. The most important ionic change is a reduction in L-type Ca2+ current, which reduces action potential duration (APD) and APD adaptation to rate. AF-induced changes in ion channel function appear to be due both to rapid voltage- and time-dependent alterations in channel availability caused by tachycardia and to slower downregulation of messenger RNA concentrations encoding alpha-subunits of specific ion channels. Atrial remodeling likely contributes importantly to a wide variety of clinical phenomena of previously unrecognized mechanism, including atrial dysfunction after cardioversion of AF, the increasing resistance to therapy of longer-standing AF, the association of AF with other forms of supraventricular tachyarrhythmia and the tendency of paroxysmal AF to become chronic. The present paper reviews the state of knowledge regarding the mechanisms and clinical consequences for AF of atrial remodeling caused by rapid atrial activation.     

The Role of Atrial Electrical Remodeling in the Progression of Focal Atrial Ectopy to Persistent Atrial Fibrillation

Although atrial fibrillation- (AF) induced changes in atrial refractoriness (atrial electrical remodeling) have been demonstrated in a number of different animal models, the clinical significance of this process is unknown. We describe a patient in whom there has been documented progression of atrial ectopy to persistent AF accompanied by evidence of atrial electrical remodeling, with reversal of remodeling following successful ablation of the focal source of AF. A second patient with focal AF, but with a "nonfocal" appearance on the ECG, is also described. These cases illustrate: (1) the possibility that a significant proportion of younger patients with idiopathic persistent AF may well have a focal source as the underlying abnormality; and (2) atrial electrical remodeling reverses following ablation of the underlying source.     

The potential role of thiazolidinediones in atrial fibrillation

Thiazolidinediones (TZDs) represent insulin sensitizing drugs that are being increasingly used for the treatment of type 2 diabetes. These agents have also pleiotropic properties that possibly contribute to their favorable cardiovascular effects. In particular, TZDs have anti-inflammatory and anti-oxidant potential while they modulate cardiovascular remodeling. On the other hand, atrial electrical and structural remodeling constitutes the substrate for atrial fibrillation (AF) development and perpetuation. Of note, inflammation and oxidative stress have been recently implicated in the pathogenesis of AF while non-channel blocking drugs with pleiotropic properties, including anti-inflammatory and anti-oxidant, seem to favorably affect atrial remodeling. It is therefore reasonable to assume that TZDs may have a role in the management of AF. Despite some limited observations, no study to date has examined the effect of TZDs therapy on AF development. In addition, the role of these agents in atrial remodeling has not been clarified yet.     

β3肾上腺素能受体与心房颤动心肌代谢重构的研究进展

心房颤动（atrial fabrillation,AF）时,心房发生代谢重构,可促进AF的发生及维持,二者相互促进形成恶性循环,可进一步加重AF。研究表明β3肾上腺素能受体（β3-Adrenoceptor,β3-AR）与AF电重构、结构重构密切相关,但关于β3-AR对AF心肌能量代谢重构作用的报道较少。本综述旨在探讨β3-AR与AF心肌能量代谢重构的关系,为临床AF的防治寻找新靶点。     

老年阻塞性睡眠呼吸暂停综合征患者房颤发生机制和治疗的研究进展

阻塞性睡眠呼吸暂停(OSA)是老年常见的睡眠呼吸异常综合征。近年研究发现,OSA患者心房颤动(AF)的发生率明显增加,OSA可能通过代谢异常、组织重构、炎症反应和自主神经失衡等机制诱发心房结构改变和电重构,促进AF发生和发展。OSA患者AF的非药物治疗包括持续气道正压(CPAP)通气治疗、神经刺激、口腔装置和悬雍垂腭咽成形术等,药物治疗包括抗心律失常药物、抗炎药物等;OSA的早期发现和积极治疗可降低AF的发生率。     

Diabetes Mellitus and Atrial Remodeling: Mechanisms and Potential Upstream Therapies

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM‐related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.     

Electrical Remodeling in Atrial Fibrillation

Electrical remodeling refers to any change in electrical function that promotes atrial fibrillation (AF). A key advance in understanding the mechanisms of AF has been the identification of ion channels, gap junctions and regulators of intracellular Ca(2+) homeostasis as the molecular determinants of abnormal atrial electrical activity, and how these are modified in AF. This review focuses on the cellular and molecular basis of altered electrical properties of the atria in AF, with the goal of providing new insights into the potential molecular mechanisms and the identification of putative targets for antiarrhythmic therapy.