心脏诱导的研究

对心脏发育调控机制的认识是从观察两栖动物和鸟类的胚胎学过程开始的.心脏的诱导调控一直是人们研究的热点.从心脏的形态发生,心脏诱导和心脏的分子标识等3个方面对最近的一系列研究结果进行了综述.     

心肌细胞周期调控的研究进展

尽管分子心脏学在很多方面已经取得了较大的进展,但是有关心脏形成细胞的起源、诱导心脏发生的机理、胚胎期和成人期心肌细胞增殖的调控途径仍然不是很清楚.在最近的研究中,人们对心肌细胞周期调控已有所了解.主要就心肌细胞周期活动和成人心肌细胞发生的研究进展进行了综述.     

基于心脏电生理模型的心律失常机制研究进展

揭示发病机制是心律失常诊断、治疗、药物研发和设备设计的关键.整合当前在心脏分子生物学、生物化学、生理学及解剖学方面的最新成果,构建从离子通道、心肌细胞、心肌纤维、心肌组织、心脏器官到躯体各个层次的多尺度多模态心脏电生理模型,用于系统研究微观局部变化发生、发展、转化为宏观心律失常表现的过程,将彻底改变传统从基因突变、蛋白质表达、细胞电生理、临床表现单独研究心律失常的方式,实现微观与宏观研究的统一,使心脏电生理模型成为系统研究心律失常发病机制的有力手段.本文综述了心脏电生理模型的构建方法和研究进展,讨论了多尺度心脏电生理模型在揭示心律失常机制研究中的作用和地位,给出了基于心脏电生理模型心律失常研究的挑战和重要发展方向.     

microRNA在心脏发育与疾病中功能研究进展

microRNAs(miRNAs)是一种基因组编码的小RNA,它们通过与目标mRNA分子的3'端非编码区域(3'UTR)互补配对导致mRNA分子稳定性和翻译受到抑制,在调节细胞增殖、凋亡、分化和肿瘤发生等多种生物学过程中起重要作用.心脏是人体的重要器官之一,其发育与疾病发生过程非常复杂,受到多种信号通路的调控.近期的研究表明,miRNAs在心脏的发生发育与疾病过程中都发挥着重要的作用,本文将对这方面的研究进展作一综述.     

心管发生的分子机制

心管的发生是心脏发育早期最重要的事件之一.它由左右两团心脏前体细胞逐渐相互靠拢合并成一条位于腹侧正中的线性心管,然后再进行环化和房室化.心管发生的分子机制与两个方面有关:其一为心脏前体细胞的迁移,在斑马鱼中8个基因与之有关;其二为心管的装配,has等基因与之有关.     

心脏间隔的形成

心脏形态的建成包括了腔室的形成和间隔的形成两个部分,而心脏间隔的出现又使得心脏从单腔室器官发育成为四腔室的成熟器官.在人类心脏发育过程中,心脏间隔的发生是在胚胎发育的第4周至第7周,在这个过程中,心脏的袢环化以及腔室的逐渐建成,也促进了心脏间隔的形成.心肌层在房室腔的建成中充当了重要的角色,但是研究表明它在心脏间隔的发生中却没有起到实质性的作用,相反对于心外间充质组织,人们开始重新认识它在心脏间隔发生中的意义.     

心脏外科术后心房颤动的研究进展

心房颤动(Atrial Fibrillation,AF)是心脏术后较常见的并发症之一.它不但增加患者的住院天数和住院费用,而且还可以引起术后栓塞、脑血管以外和心功能衰竭的发生.研究发现术前高龄、左房增大、术后停用β受体阻滞剂等是心脏术后房颤发生的危险因素.现对其发生的危险因素、预防策略和药物治疗进行总结.     

脊椎动物心脏形态发育的转录调控

转录因子以组织特异性和数量的方式调节基因的表达,是胚胎发育中的主要调节因子.目前已经鉴定了一些特异性调节心脏基因的转录因子,最近又发现显性遗传转录因子的突变能引起人类先天性心脏缺陷,将心脏发育转录因子的研究直接与医学联系起来.尽管这方面的研究已经很广泛了,但心脏发育的转录调控仍不很清楚.本文对心脏转录因子及其作用研究的最新进展进行了综述.     

心脏的左右不对称发育

心脏是脊椎动物发育过程中最早形成的器官之一,心管向右环化打破了左右对称的格局,是左右分化的第一个重要标志.不对称的心管环化和心脏腔室的形态发生是一个相当复杂的过程,人们对其分子机制,特别是心脏定位和不对称发育机理的了解还相当有限.为了探讨心脏的左右不对称发育,重点从形态学和分子水平对近期的研究作了简要的概述.     

线粒体稳态失衡与心脏衰老及相关疾病

随着年龄的增长,衰老的心脏会发生左室肥厚、舒张功能不全、瓣膜功能下降、心肌纤维化增加、电传导异常等病理变化.线粒体作为真核细胞中调控代谢的关键细胞器,是细胞内合成ATP的重要场所.由于心脏一刻不停地收缩需要大量ATP提供能量,线粒体稳态对于维持正常的心脏功能至关重要,而线粒体稳态失衡则会导致心脏功能发生异常.本文主要阐述了衰老心脏中线粒体的异常变化,探讨了线粒体形态与数量变化、线粒体代谢异常、线粒体质量控制失衡、线粒体基因组和转录组改变等线粒体稳态失衡在常见衰老相关心脏疾病发生发展中的重要作用,总结了靶向线粒体干预衰老相关心脏疾病的现状与前景,为研究线粒体相关心脏疾病的细胞分子机制,治疗衰老相关的心脏疾病提供新的思路.     

Mapping cardiac surface mechanics with structured light imaging

Cardiovascular disease often manifests as a combination of pathological electrical and structural heart remodeling. The relationship between mechanics and electrophysiology is crucial to our understanding of mechanisms of cardiac arrhythmias and the treatment of cardiac disease. While several technologies exist for describing whole heart electrophysiology, studies of cardiac mechanics are often limited to rhythmic patterns or small sections of tissue. Here, we present a comprehensive system based on ultrafast three-dimensional (3-D) structured light imaging to map surface dynamics of whole heart cardiac motion. Additionally, we introduce a novel nonrigid motion-tracking algorithm based on an isometry-maximizing optimization framework that forms correspondences between consecutive 3-D frames without the use of any fiducial markers. By combining our 3-D imaging system with nonrigid surface registration, we are able to measure cardiac surface mechanics at unprecedented spatial and temporal resolution. In conclusion, we demonstrate accurate cardiac deformation at over 200,000 surface points of a rabbit heart recorded at 200 frames/s and validate our results on highly contrasting heart motions during normal sinus rhythm, ventricular pacing, and ventricular fibrillation.     

The actions of insulin on cardiac contractility

This review summarizes the effects of insulin on cardiac contractility of the normal, failing, anoxic and ischemic heart. In animal experiments under aerobic conditions a variety of effects of insulin on cardiac contractile force have been described which are frequently contradictory. The use of different insulin preparations of unknown purity make the interpretation of these findings rather difficult. The protective effects of insulin in the isolated heart on the rate of production of spontaneous heart failure require both glucose and insulin for maximal effect and are probably related to an improved cardiac carbohydrate utilization produced by insulin. Other cardiac effects of insulin independent of glucose could be due to ionic readjustments produced by insulin which are glucose independent.     

Segmentation of cardiac sound signals by removing murmurs using constrained tunable-Q wavelet transform

The automatic segmentation of cardiac sound signals into heart beat cycles is generally required for the diagnosis of heart valve disorders. In this paper, a new method for segmentation of the cardiac sound signals using tunable-Q wavelet transform (TQWT) has been presented. The murmurs from cardiac sound signals are removed by suitably constraining TQWT based decomposition and reconstruction. The Q-factor, redundancy parameter and number of stages of decomposition of the TQWT are adapted to the desired statistical properties of the murmur-free reconstructed cardiac sound signals. The envelope based on cardiac sound characteristic waveform (CSCW) is extracted after the removal of low energy components from the reconstructed cardiac sound signals. Then the heart beat cycles are derived from the original cardiac sound signals by mapping the required timing information of CSCW which is obtained using established methods. The experimental results are included in order to show the effectiveness of the proposed method for segmentation of cardiac sound signals in comparison with other existing methods for various clinical cases.     

Sweet,yet underappreciated: Proteoglycans and extracellular matrix remodeling in heart disease

Extracellular matrix remodeling is extensive in several heart diseases and hampers cardiac filling, often leading to heart failure. Proteoglycans have over the last two decades emerged as molecules with important roles in matrix remodeling and fibrosis in the heart. Here we discuss and review current literature on proteoglycans that have been studied in cardiac remodeling. The small leucine rich proteoglycans (SLRPs) are located within the extracellular matrix and are organizers of the matrix structure. Membrane-bound proteoglycans, such as syndecans and glypicans, act as receptors and direct cardiac fibroblast signaling. Recent studies indicate that proteoglycans are promising as diagnostic biomarkers for cardiac fibrosis, and that they may provide new therapeutic strategies for cardiac disease.     

Circadian variation of abnormal heart beats in an elderly population and their relation to sudden cardiac death.

The relationships between the circadian variation of abnormal heart beats and the circadian variation in sudden cardiac death warrant further discussion for the high correlations demonstrated here are difficult to ignore. In the healthy group abnormal beats showed a high correlation of their circadian variation with that of sudden cardiac death which is independent of heart rate. As a result the conclusion that the relationship of the circadian variations of abnormal heart beats and sudden cardiac death is merely dependent on a mutual dependence on activity is not supported here. The present data illustrates a strong association between arrhythmias and sudden cardiac death. The relationship of sudden cardiac death with abnormal heart beats demonstrated here, however, cannot confirm a causal role of the latter on the former for both may be responding to circadian variations of some underlying mechanism such as ischemia. Additionally the population studied here, although relatively comparable in terms of living conditions and other significant factors, was not strictly age-matched with those from the sudden cardiac death study warranting further caution in interpreting the association demonstrated here. The results from the unhealthy group, although somewhat limited, indicate that cardiovascular morbidity may alter the relationship of sudden cardiac death and abnormal heart beats. Such a result could be explained by the presence of other forms of heart disease which could be responsible for sudden cardiac death in the unhealthy group. An interesting question to ask concerning the data presented above is whether or not significant circadian variations in in the frequency of abnormal heart beats could have been demonstrated when exogenous factors such as meal times and activity were altered. The data on in hospital sudden cardiac death indicates that the circadian variation in sudden cardiac death is significantly altered by the radical changes in routine which accompany hospitalization. If the relationship between the circadian variation of sudden cardiac death and abnormal heart beats is as strong as the results presented here indicate, it is likely that the alteration of such exogenous factors would also change the circadian variation of abnormal heart beats. The results of the present study indicate that both the circadian variation in abnormal heart beats, and its relationship to sudden cardiac death, warrant further study.     

Cardiac GPCRs: GPCR signaling in healthy and failing hearts

G protein-coupled receptors (GPCRs) are widely implicated in human heart disease, making them an important target for cardiac drug therapy. The most commonly studied and clinically targeted cardiac GPCRs include the adrenergic, angiotensin, endothelin, and adenosine receptors. Treatment options focusing on the complex and integrated signaling pathways of these GPCRs are critical for the understanding and amelioration of heart disease. The focus of this review is to highlight the most commonly studied and clinically targeted cardiac GPCRs, placing emphasis on their common signaling components implicated in cardiac disease.     

Normal and abnormal development of the cardiac conduction system; implications for conduction and rhythm disorders in the child and adult

The cardiac conduction system is a specialized network that initiates and closely coordinates the heart beat. Cardiac conduction system development is intricately related to the development and maturation of the embryonic heart towards its four-chambered form, as is indicated by the fact that disturbed development of cardiac structures is often accompanied by a disturbed formation of the CCS. Electrophysiological studies have shown that selected conduction disturbances and cardiac arrhythmias do not take place randomly in the heart but rather at anatomical predilection sites. Knowledge on development of the CCS may facilitate understanding of the etiology of arrhythmogenic events. In this review we will focus on embryonic development of the CCS in relation to clinical arrhythmias, as well as on specific cardiac conduction abnormalities that are observed in patients with congenital heart disease.     

Ketone metabolism in the failing heart

The high energy demands of the heart are met primarily by the mitochondrial oxidation of fatty acids and glucose. However, in heart failure there is a decrease in cardiac mitochondrial oxidative metabolism and glucose oxidation that can lead to an energy starved heart. Ketone bodies are readily oxidized by the heart, and can provide an additional source of energy for the failing heart. Ketone oxidation is increased in the failing heart, which may be an adaptive response to lessen the severity of heart failure. While ketone have been widely touted as a “thrifty fuel”, increasing ketone oxidation in the heart does not increase cardiac efficiency (cardiac work/oxygen consumed), but rather does provide an additional fuel source for the failing heart. Increasing ketone supply to the heart and increasing mitochondrial ketone oxidation increases mitochondrial tricarboxylic acid cycle activity. In support of this, increasing circulating ketone by iv infusion of ketone bodies acutely improves heart function in heart failure patients. Chronically, treatment with sodium glucose co-transporter 2 inhibitors, which decreases the severity of heart failure, also increases ketone body supply to the heart. While ketogenic diets increase circulating ketone levels, minimal benefit on cardiac function in heart failure has been observed, possibly due to the fact that these dietary regimens also markedly increase circulating fatty acids. Recent studies, however, have suggested that administration of ketone ester cocktails may improve cardiac function in heart failure. Combined, emerging data suggests that increasing cardiac ketone oxidation may be a therapeutic strategy to treat heart failure.     

Cardiac GPCRs: GPCR signaling in healthy and failing hearts

G protein-coupled receptors (GPCRs) are widely implicated in human heart disease, making them an important target for cardiac drug therapy. The most commonly studied and clinically targeted cardiac GPCRs include the adrenergic, angiotensin, endothelin, and adenosine receptors. Treatment options focusing on the complex and integrated signaling pathways of these GPCRs are critical for the understanding and amelioration of heart disease. The focus of this review is to highlight the most commonly studied and clinically targeted cardiac GPCRs, placing emphasis on their common signaling components implicated in cardiac disease.     

基于能量融合积分模型的心脏生理物理活动研究

为了更深入地了解目前靠生理实验及临床手段无法洞察的心脏三维空间的电生理运行机制,分析和表现心脏复杂的电生理活动,从而揭示心脏的生理物理特性,本研究通过人类心肌细胞的动作电位传导数学模型,结合基于心脏解剖数据所建立的真实心脏组织结构的三维空间模型,构建出精细的心脏生物物理融合模型,并将心脏在三维空间中的生物物理活动表现出来.实验结果表明,基于心脏动作电位传导的融合模型,不同时刻的动作电位传导在非匀质性组织内的三维空间中的传播位置、空间关系以及生物物理过程被清晰地显示出来,心脏研究人员从而能够以视觉感知的方式认识和深入理解人类心脏电生物物理系统的功能机制,并有助于进一步推测心脏的生理和病理反应.