心脏原位干细胞修复心肌的研究

心尖和心房内存在少量的原位干细胞,在生理情况下心脏原位干细胞(cardiac stem cells,CSCs)对于维持心肌细胞稳态有重要作用.该文对CSCs用于心脏再生治疗的优势,体外扩增CSCs的技术,心脏修复机制(包括分化机制和旁分泌机制),各种心脏疾病中CSCs的变化以及目前CSCs治疗遇到的问题作一简介.     

与心律失常相关的microRNAs研究现状

microRNAs(miRNAs)是内源性非编码小RNA,长度约为20～23个核苷酸。miRNAs通过与靶mRNA的互补配对而对基因在转录后水平上的表达进行负调控,导致mRNA的降解或翻译抑制。近年的研究发现,miRNAs在心血管系统高度表达,是心肌细胞功能的重要调节因子,对心律失常的发生起重要作用。多个miRNAs如miR-1、miR-133及miR-208通过不同离子通道的功能来影响心肌电位变化及心脏传导系统,进一步引起心律失常。此外,由于miRNAs与多种心血管系统疾病的发病有重要关系,它可能成为心血管领域一个新的治疗靶标。     

心脏干细胞活化相关分子在心血管疾病中的作用

胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、肝细胞生长因子(Hepatocyte growth factor,HGF)在许多干细胞中都发挥积极作用,心脏干细胞(cardiac stem cells,CSCs)作为研究比较多的对心肌缺血性疾病有重要治疗作用的细胞也日益受到重视。近年来发现CSCs活化对于治疗的意义非常明确,而IGF/HGF是激发其活化态的重要分子,并且二者作用的信号通路有一定重叠,对于研究CSCs活化的分子机制有重要作用。二者还可以促进CSCs的迁移、促进增殖、抗凋亡等。     

航空异常环境因素对心脏干细胞的影响

随着对干细胞研究的不断深入，干细胞治疗心脏疾病的作用机制也越来越明晰。心脏干细胞（CSCs）具有组织特异性和心系定向分化潜能，因此，在心脏疾病治疗方面较其他种类的干细胞具有明显优势。根据CSCs表达标记物的不同，可进一步将其分为不同的族群。本文旨在介绍不同族群CSCs的表型特征、分化潜能及临床应用前景，并重点关注缺氧、辐射等航空异常环境因素对CSCs功能和状态的影响。     

miR-367影响冠心病不稳定斑块形成的机制研究

目的:探讨miR-367影响冠心病不稳定斑块形成的机制。方法:收集急性心肌梗死(AMI)和稳定性心绞痛(SA)的汉族和维吾尔族患者及健康对照者血浆样本各60例,采用高通量miRNA芯片检测患者血浆差异表达的miRNAs;通过PicTar、TargetScan、miRWalk数据库分析预测候选miRNAs的靶基因并通过DAVID数据库筛选确定目的基因;荧光定量PCR检测候选miRNAs在各组患者中的表达水平;通过构建人脐静脉内皮细胞(HUVEC)的候选miRNAs敲低和过表达细胞系验证候选miRNAs对血管生成的作用;使用双荧光素酶报告基因实验检测候选miRNAs与目的基因的靶向性,并通过Western Blot验证候选miRNAs对靶基因蛋白表达的影响。结果:芯片结果显示,miR-367在两民族AMI患者中表达下调;DAVID筛选预测miR-367与VEGFR-2存在靶向结合位点;较对照组而言,AMI患者miR-367表达显著降低(P<0.001);干扰HUVEC细胞中miR-367的表达显著促进了细胞的增殖和迁移,过表达miR-367后HUVEC细胞功能受到明显阻滞;双荧光素酶报告实验显示野生型VEGFR-2基因共转染miR-367过表达载体后荧光素酶活性较对照组显著降低;敲低HUVEC细胞中miR-367表达后,细胞内VEGFR-2蛋白表达显著升高。结论:血浆循环miR-367在AMI患者中表达减少,miR-367可能通过负调控VEGFR-2的表达对血管内皮细胞产生调控作用。     

microRNAs在心脏疾病中的研究进展

microRNAs(miRNAs)是能够调控基因表达的小核苷酸序列。相关研究表明miRNA可维持体内环境稳态,调控真核细胞的生理功能,参与到多种病理途径过程。许多研究表明,心脏疾病的发生发展与miRNAs的调控息息相关,因而,近年对miRNAs在心脏疾病方面的研究得到迅猛发展。本文对miRNA在心脏疾病中的作用进行了综述,并探讨了相关的分子机制,旨在寻找治疗心脏疾病的新靶点。     

microRNAs与室性心律失常

微小RNA(microRNAs,miRNAs)是内源性非编码小RNA之一,通过调控基因转录后的表达水平在人体多种生物学过程中扮演着重要的角色。研究表明,miRNAs与室性心律失常的发生密切相关,诸如miR-133、miR-1、miR-17-92、miR-130a、miR-19b、miR-223-3-p均参与室性心律失常的发生发展,由于miRNAs存在于血液循环中,因此有望成为室性心律失常预警标记物之一。     

系统性红斑狼疮患者循环微小RNAs差异表达的初步分析

目的 检测系统性红斑狼疮(SLE)患者血浆中差异表达的微小RNAs(miRNAs),为寻求一种新的无创性SLE生物标志物奠定基础.方法 采用Agilent human miRNA芯片检测并筛选出SLE患者与健康人血浆中表达丰度有显著变化miRNA,并通过实时荧光定量聚合酶链反应(RT-qPCR)对部分差异表达基因进行验证.2组间的比较用独立样本的t检验.结果 MiRNAs芯片检测发现,SLE患者与健康对照间存在明显差异的循环miRNAs共有51个,其中19个上调,32个下调;RT-qPCR对其中4个上调(miR- 126、miR-21、miR-223和miR-451)和3个下调(miR-125a-3p、miR-146a和miR-155)循环miRNAs的验证结果与芯片数据所示具有较好的一致性.结论 SLE患者和健康人体内循环miRNAs的表达谱存在着明显差异,这些差异的循环miRNAs可作为一种潜在的SLE候选生物标志物.     

MicroRNA-150在肿瘤发生发展中作用的研究进展

MicroRNAs (miRNAs)是一类长约18 ～ 22个核苷酸的小分子单链非编码RNA分子(non-coding RNA,ncRNA),它通过破坏靶mRNA的稳定性或者抑制其翻译的方式对基因的表达进行调控[1].目前的研究认为,miRNA作为转录后调控分子,参与了人类癌症的发生和发展过程.通过分析miRNA表达谱有助于对人类肿瘤的诊断、分期、预后及治疗效果等方面进行评估[2-3].自1993年首次在秀丽新小杆线虫中发现了lin-4 RNA以来,越来越多的miRNAs和它们各自的作用靶点及相应功能被人们发现并研究[4].miR-150作为miRNAs家族中的一员,在肿瘤性疾病和非肿瘤性疾病中均具有重要的作用.现就miR-150在肿瘤发生发展中的作用研究进展作一综述.     

内源性心脏干/祖细胞活化的研究进展

随着现代生活方式的改变和老龄化的问题,心血管疾病已成为威胁人类健康的第一杀手。然而当前医疗诊治技术仍难以彻底改善心肌梗死后缺血性心肌病及心力衰竭患者的预后。干细胞的出现为心肌再生带来了新的希望。与其他成体干细胞相比,内源性心脏干细胞(CSCs)具有分化成心肌细胞和血管内皮细胞的潜能,可对受损心肌起到明显的修复作用。研究发现,心肌梗死后内源性CSCs的激活与多种因素有关。最近几年,内源性CSCs活化介导的心肌修复引起了研究人员极大的兴趣。本文将对CSCs激活所涉及的主要途径进行论述,以深化对内源性CSCs功能的理解。     

Role of microRNAs in stem/progenitor cells and cardiovascular repair

MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in differentiation and self-renewal of pluripotent stem cells, as well as in differentiation of cardiovascular lineage cells. Several miRNAs have been demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in embryonic stem cells, thereby promoting embryonic stem cell differentiation. Furthermore, targeting of different miRNAs promotes reprogramming towards induced pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell differentiation and phenotype regulation, and miR-143 and miR-145 play a particularly important role in this respect. Notably, these miRNAs are down-regulated in several cardiovascular disease states, such as in atherosclerotic lesions and vascular neointima formation. MicroRNAs are critical regulators of endothelial cell differentiation and ischaemia-induced neovascularization. miR-126 is important for vascular integrity, endothelial cell proliferation and neovascularization. miR-1 and miR-133 are highly expressed in cardiomyocytes and their precursors and regulate cardiomyogenesis. In addition, miR-499 promotes differentiation of cardiomyocyte progenitor cells. Notably, miRNA expression is altered in cardiovascular disease states, and recent studies suggest that dysregulated miRNAs may limit cardiovascular repair responses. Dysregulation of miRNAs may lead to an altered function and differentiation of cardiovascular progenitor cells, which is also likely to represent a limitation of autologous cell-based treatment approaches in these patients. These findings suggest that targeting of specific miRNAs may represent an interesting novel opportunity to impact on endogenous cardiovascular repair responses, including effects on stem/progenitor cell differentiation and functions. This approach may also serve to optimize cell-based treatment approaches in patients with cardiovascular disease.     

Synergy of microRNA and stem cell: a novel therapeutic approach for diabetes mellitus and cardiovascular diseases

MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding, endogenous RNA, which are transcribed from either intergenic, intronic or polycistronic regions and modulate gene expression through mRNA degradation or translational repression. They are fine tuners of biological processes and have recently emerged as biomarkers and therapeutic targets of cardiovascular diseases. Several miRNAs regulate stem cell for differentiation, proliferation and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells having tremendous potential for regenerative therapy. The current therapeutic approach is unable to cope up with rapidly increasing rates of diabetes and cardiovascular diseases. The empirical and clinical evidences revealed that transplantation of exogenous stem cells can regenerate beta cells in diabetic patients and myocardium in patients with myocardial infarction. Nevertheless, the major limitation of stem cell therapy is unpredictable behavior of exogenous stem cells that incur few reports of teratoma and cancer after transplantation. Therefore, understanding the regulation of newly transplanted stem cells into the foreign body is a major challenge to translational research / clinical trail. Since miRNA plays pivotal role in the fine regulation of proliferation and differentiation of stem cells, investigations on the regulation of miRNA in transplanted stem cells in a specific micro-environment that houses the stem cell is indispensable. Additionally, the inhibition or over expression of specific miRNAs in the niche surrounding the stem cell will be crucial for maintaining the specific lineage of exogenous stem cells. This review embodies major advancement in the field of miRNA biogenesis and its regulatory mechanisms, role of different miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular diseases. It also provides insights into the novel future therapy, where synergistic approach for manipulating miRNAs and stem cells will emerged as a potential treatment for diabetes and cardiovascular diseases.     

microRNA-1和microRNA-133参与小鼠诱导多能干细胞向心肌的分化

目的 研究microRNA-1（miRNA-1）和microRNA-133（miRNA-133）对小鼠诱导多能干细胞（miPSCs）向心肌分化的影响。方法 RT-PCR分析miPSC分化过程中microRNA-1和microRNA-133的表达变化；microRNA-1和micro-133反义寡核苷酸转染miPSCs，增强miRNA-1和miRNA-133表达；并按照转染分子的不同，将细胞分为对照组（添加miRNA-U6）、miRNA-1组、miRNA-133组和miRNA-1+miRNA-133组。RT-PCR、q-PCR和免疫荧光化学染色检测miRNA转染并诱导miPSCs分化后，各组细胞内miRNA-1和miRNA-133的表达变化以及心肌细胞相关特异性基因和蛋白的变化。结果 miPSCs心肌分化过程中miRNA-1，miRNA-133的表达具有差异性，均在后期有显著增高（P<0.01）；在分化过程中单独过表达miRNA-1 和miRNA-133对心肌的分化并未有促进作用，但共表达miRNA-1 和miRNA-133后，却显著增加心肌细胞的搏动数量和心肌基因的表达，并且促进了心肌细胞成熟。结论 miRNA-1和miRNA-133通过协同作用促进miPSCs体外分化为心肌细胞，显著提高 miPSC 向心肌细胞定向分化效率。     

miR-126与心血管疾病关系的研究进展

微小核糖核酸(microRNAs,miRNA)是一类内源性高度保守的非编码小分子RNA,其可通过降解信使RNA并抑制其翻译在转录水平调控靶基因的表达,参与细胞生长、发育、分化和增殖等多个生命过程。MicroRNAs-126(miR-126)是一种内皮特异性miRNA,与高血压、动脉粥样硬化、冠心病、心力衰竭等心血管疾病密切相关。近期研究表明,miR-126能显著影响心血管疾病的发生、发展和疾病的预后。本文就miR-126与心血管疾病的关系进行综述。     

Overview of recent advances in molecular cardiology

Molecular cardiology is a new and fast-growing area of cardiovascular medicine that aims to apply molecular biology techniques for the mechanistic investigation, diagnosis, prevention and treatment of cardiovascular disease. As an emerging discipline, it has changed conceptual thinking of cardiovascular development, disease etiology and pathophysiology. Although molecular cardiology is still at a very early stage, it has opened a promising avenue for understanding and controlling cardiovascular disease. With the rapid development and application of molecular biology techniques, scientists and clinicians are closer to curing heart diseases that were thought to be incurable 20 years ago. There clearly is a need for a more thorough understanding of the molecular mechanisms of cardiovascular diseases to promote the advancement of stem cell therapy and gene therapy for heart diseases. The present paper briefly reviews the state-of-the-art techniques in the following areas of molecular cardiology: gene analysis in the diseased heart; transgenic techniques in cardiac research; gene transfer and gene therapy for cardiovascular disease; and stem cell therapy for cardiovascular disease.     

非酒精性脂肪性肝病患者血清中循环microRNAs表达水平及意义

目的研究microRNAs(miRNAs)在非酒精性脂肪性肝病(NAFLD)患者血清中的表达水平和意义。方法选择NAFLD患者78例(NAFLD组)和非NAFLD人群58例(对照组)。采集入组人群血清,提取总RNA,应用qRT-PCR方法对血清中miR-21、miR34a、miR-122及miR-451表达水平进行检测;分析miRNAs血清表达水平与脂肪变性程度之间的关系。结果两组人群血清中miR-145(P=3.290)和miR21(P=1.570)表达水平无显著变化;miR-451(P=0.0309)、miRNA-122(P=0.0083)和miR-34a(P=0.0032)表达水平显著升高。NAFLD组患者根据肝脏脂肪变性程度分为轻度(46例)和重度(32例),miRNA-122(P=0.0062)和miRNA-34a(P=0.0044)的表达水平随脂肪变性程度的增加而显著升高。结论 NAFLD患者较健康人群血清miR-21、miR-34a、miR-122及miR-451表达水平升高,特别是miR-34a和miR-122可以作为NAFLD诊断的一个生物学标志分子。