线粒体自噬在心血管疾病中的作用

自噬对于组成心血管系统细胞(如心肌细胞、内皮细胞和血管平滑肌细胞等)的细胞内稳态和生理功能的维持具有重要作用。线粒体自噬是以损伤的线粒体作为自噬底物的一种选择性自噬。由于线粒体是生物能量的主要来源且心血管系统对能量要求较高,线粒体自噬在心血管稳态的维持中尤为重要。研究证实线粒体自噬在心肌梗死、心力衰竭和动脉粥样硬化等疾病中扮演重要角色。本文概述了线粒体自噬的主要调控通路,并阐述了线粒体自噬与心血管疾病之间的密切联系。     

辛伐他汀保护缺血-再灌注损伤心肌的线粒体蛋白质组学研究

目的建立大鼠心肌缺血-再灌注损伤模型,通过蛋白质组学的方法研究辛伐他汀对大鼠缺血-再灌注损伤心肌线粒体代谢的保护作用。方法将大鼠随机分为辛伐他汀干预组(n=14)和生理盐水对照组(n=14),建立缺血-再灌注损伤模型,通过伊文思蓝和TTC染色评估梗死面积,提取大鼠左心室心肌线粒体蛋白行双向凝胶电泳,应用质谱分析鉴定差异蛋白点。结果辛伐他汀组和对照组相比,梗死区与危险区(梗死区+缺血区)的比值有统计学差异(29.4%±8.4%vs57.7%±6.5%,P0.0001);梗死面积与左室面积的比值有统计学差异(15.9%±5.6%vs29.0%±8.9%,P=0.012)。双向凝胶电泳图谱分析有19个蛋白点的表达有差异,质谱鉴定了9种差异蛋白,相比对照组,辛伐他汀组4个蛋白表达上调:三功能酶亚基α(线粒体前体)、电子转移黄素蛋白脱氢酶、肌动蛋白α(心肌)、细胞色素c氧化酶亚基5A亚单位(线粒体前体);5个蛋白表达下调:L-乳酸脱氢酶B链、异柠檬酸脱氢酶[NAD]α亚基(线粒体前体)、α晶状体蛋白B链、内膜蛋白(线粒体)、肌动蛋白类似物(细胞质)。结论辛伐他汀组大鼠心肌在缺血-再灌注损伤后,心肌梗死面积显著减少,辛伐他汀改变线粒体呼吸链、能量代谢等途径上的蛋白,为阐明辛伐他汀保护缺血再灌注损伤提供了理论依据。     

线粒体相关内质网膜（MAMs）在心血管疾病中的研究进展

作为内质网和线粒体接触的结构,线粒体相关内质网膜（mitochondria-associated endoplasmic reticulum membranes,MAMs）可通过膜结构上的分子促进两种细胞器的物质和信号的交流。目前MAMs在脂质的生物合成与转运、钙稳态的维持、ROS的产生以及自噬过程中的角色逐步被证实。研究表明,MAMs在一些心血管疾病如心力衰竭、心肌缺血再灌注损伤、动脉粥样硬化的发生中十分重要。本文介绍了MAMs的分离和观察方法以及在细胞稳态维持中的作用,并讨论了MAMs在一些心血管疾病中的作用。     

线粒体动力学异常与相关心血管疾病

线粒体是心肌能量代谢的主要场所,其通过分裂和融合的动态平衡维持正常的形态和功能.线粒体分裂和融合的动态转换称为线粒体动力学,受线粒体融合和分裂相关蛋白等多种蛋白调控.线粒体动力失衡可引起心脏结构和功能的紊乱,参与扩张型心肌病、缺血再灌注损伤、脓毒性心肌病、糖尿病心肌病和动脉粥样硬化等心血管疾病的发生和发展.维持线粒体动...     

线粒体通透性转换孔与心肌缺血再灌注损伤

线粒体在细胞的存活和死亡中起着重要的作用。线粒体通透性转换孔（MPTP）是线粒体内外信息交流的中心枢纽其功能的发挥依赖于其自身的开放状态。大量研究表明，MPTP在照血再灌注损伤中扮演着重要角色MPTP开放是照血再灌注后细胞坏死和凋亡的共同通路。     

线粒体途径保护心肌缺血再灌注损伤的研究进展

线粒体是细胞能量代谢和细胞内信号传导过程的关键细胞器,参与多种复杂信号介导的细胞生存和死亡。线粒体功能障碍及由此产生的氧化应激与心肌缺血再灌注损伤密切相关,保护线粒体功能将有助于减缓心肌损伤的严重程度或进展。最近,线粒体生物学进展启发人们研制作用于线粒体的选择性靶向药物,保护心肌缺血再灌注损伤。本文就此做一综述。     

辣椒素减轻肾缺血再灌注损伤的线粒体相关机制

目的探讨辣椒素对大鼠肾缺血再灌注损伤的保护作用及线粒体相关作用机制。方法将50只雄性SD大鼠分成假手术组、肾缺血再灌注损伤组和辣椒素低、中、高剂量组。采用夹闭双侧肾蒂构建肾缺血再灌注损伤模型。肾缺血45 min,再灌注24 h,过量麻醉法处死大鼠,收集肾脏和血清。检测血清肌酐(SCr)、血尿素氮(BUN)、肾脏组织病理形态和细胞凋亡,测定线粒体三磷酸腺苷(ATP)和丙二醛(MDA)含量以及Ca~(2+)-ATP酶、Na~+-K~+-ATP酶、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)活性。结果辣椒素干预可减少SCr和BUN含量,降低肾组织病理改变和细胞凋亡,增加线粒体Ca~(2+)-ATP酶、Na~+-K~+-ATP酶、CAT、GPx和SOD酶活性以及ATP的含量,但减少MDA的水平。结论辣椒素对肾缺血再灌注损伤有保护作用,其作用呈浓度效应,机制与抑制线粒体脂质过氧化相关。     

线粒体通透性转运孔与心肌缺血预处理

线粒体通透性转运孔(Mitochondrial permeability transition pore,MPTP)是位于线粒体内外膜之间的多个蛋白质复合体.本文综述了MPTP生理病理学功能\在缺血-再灌注损伤中的作用及与缺血预处理的相关性.     

线粒体融合、分裂与心肌缺血再灌注损伤的研究进展

线粒体是真核细胞中一种高度动态变化的细胞器,这种网络结构的动态平衡受线粒体融合蛋白1/2(Mfn1/2),视神经萎缩蛋白1(OPA1)和动力相关蛋白1(Drp1)的调节,并对线粒体的结构和功能有着重要的作用。心肌细胞因其高耗能性而富含线粒体,线粒体融合、分裂的动态平衡在心肌细胞的能量代谢过程中起着关键的作用。目前的研究普遍认为,心肌细胞能量代谢障碍是心肌缺血再灌注损伤的始发环节。因此,由线粒体融合、分裂异常引起的功能障碍与心肌缺血再灌注损伤密切相关。     

线粒体通透性转变与缺血性脑损伤

脑缺血触发了一系列复杂的级联反应。近年来的研究发现，线粒体功能障碍在脑缺血后神经元损伤中起关键作用。脑缺血触发的多种损伤通路最后汇聚在一起，通过一个共同的分子事件--线粒体通透性转变引起细胞死亡（包括坏死和凋亡）。文章就线粒体通透性转变的特征和结构基础，其在缺血性神经元损伤中的作用和潜在的研究价值作了综述。     

Mitochondrial proteomics

Alteration of the mitochondrial proteome and altered mitochondrial function has been implicated in a variety of degenerative diseases, heart disease, aging and cancer. Based upon the human genome there is estimated to be approximately 1000 to 2000 proteins constituting the mitochondrial proteome. Despite the ability of a traditional proteomic approach involving two-dimensional gel electrophoresis (2-DE) to resolve and identify thousands of proteins in a single gel, just over 600 mitochondrial proteins have been identified and characterized at the molecular level. The limitations and recent advances of 2-DE in its ability to study mitochondrial proteins and create a database of the mitochondrial proteome is discussed, as well as the alternative methods that are being employed, including different mass spectrometry based approaches following both one-dimensional SDS-PAGE and gel-free approaches, blue native gel electrophoresis (BN-PAGE), proteome simplification by submitochondrial fractionation, and affinity chromatography. In addition, the successful application of proteomics to the investigation of some specific mitochondrial cardiomyopathies is discussed. Correspondence to: J. E. Van Eyk     

mtDNA的遗传学特征与心血管疾病

线粒体基因组(mitochondrial DNA,mtDNA)是细胞能量生成的场所。分析显示mtDNA突变通过影响线粒体的氧化应激、能量代谢等方面而参与各种心血管疾病的发生、发展。通过对mtDNA的进一步研究有助于为心血管疾病寻找病因和有效的治疗提供新思路和理论基础。文章简述mtDNA的遗传学特征以及mtDNA突变与心血管疾病(如高血压病、冠心病、心肌病、心律失常等)的关系。     

Application of proteomics in cardiovascular medicine

Proteomics is an emerging field that has the potential to uncover new therapeutic targets for the treatment and prevention of cardiovascular disease, as well as new diagnostic biomarkers for early disease detection. The basic strategy when carrying out proteomic analysis of cardiovascular disease is to compare the protein complements of diseased hearts or sera with controls. Any proteins that have altered expression between the two groups can be studied further for their involvement in disease pathogenesis. A number of steps need to be taken to identify changes in protein expression, including sample preparation, protein separation, imaging, and protein identification. Such studies are already underway in some cardiovascular conditions including dilated cardiomyopathy and atrial fibrillation. This review provides a summary of the techniques used in proteomic analysis and their application to cardiovascular research.     

Mitochondrial disease

Defects of mitochondrial metabolism cause a wide range of human diseases that include examples from all medical subspecialties. This review updates the topic of mitochondrial diseases by reviewing the most important recent advances in this area. The factors influencing inheritance, maintenance and replication of mtDNA are reviewed and the genotype-phenotype of mtDNA disorders has been expanded, with new insights into epidemiology, pathogenesis and its role in ageing. Recently identified nuclear gene mutations of mitochondrial proteins include mutations of frataxin causing Friedreich's ataxia, PINK1, DJ1 causing Parkinson's disease and POLG causing infantile mtDNA depletion syndrome, ophthalmoplegia, parkinsonism, male subfertility and, in a transgenic mouse model, premature senescence. Mitochondrial defects in neurodegenerative diseases include Parkinson's, Alzheimer's and Huntington's disease. Improved understanding of mtDNA inheritance and mutation penetrance patterns, and novel techniques for mtDNA modification offer significant prospects for more accurate genetic counselling and effective future therapies.     

Overview: the maturing of proteomics in cardiovascular research

Proteomic technologies are used to study the complexity of proteins, their roles, and biological functions. It is based on the premise that the diversity of proteins, comprising their isoforms, and posttranslational modifications (PTMs) underlies biology. Based on an annotated human cardiac protein database, 62% have at least one PTM (phosphorylation currently dominating), whereas ≈25% have more than one type of modification. The field of proteomics strives to observe and quantify this protein diversity. It represents a broad group of technologies and methods arising from analytic protein biochemistry, analytic separation, mass spectrometry, and bioinformatics. Since the 1990s, the application of proteomic analysis has been increasingly used in cardiovascular research. Technology development and adaptation have been at the heart of this progress. Technology undergoes a maturation, becoming routine and ultimately obsolete, being replaced by newer methods. Because of extensive methodological improvements, many proteomic studies today observe 1000 to 5000 proteins. Only 5 years ago, this was not feasible. Even so, there are still road blocks. Nowadays, there is a focus on obtaining better characterization of protein isoforms and specific PTMs. Consequently, new techniques for identification and quantification of modified amino acid residues are required, as is the assessment of single-nucleotide polymorphisms in addition to determination of the structural and functional consequences. In this series, 4 articles provide concrete examples of how proteomics can be incorporated into cardiovascular research and address specific biological questions. They also illustrate how novel discoveries can be made and how proteomic technology has continued to evolve.     

Status and prospects for discovery and verification of new biomarkers of cardiovascular disease by proteomics

Despite unmet needs for cardiovascular biomarkers, few new protein markers have been approved by the US Food and Drug Administration for the diagnosis or screening of cardiovascular diseases. Mass spectrometry-based proteomics technologies are capable of identifying hundreds to thousands of proteins in cells, tissues, and biofluids. Proteomics may therefore provide the opportunity to elucidate new biomarkers and pathways without a prior known association with cardiovascular disease; however, important obstacles remain. In this review, we focus on emerging techniques that may form a coherently integrated pipeline to overcome present limitations to both the discovery and validation processes.     

阿尔茨海默病的蛋白质组学研究进展

@@     

Mitochondrial DNA in osteoarthritis disease

Clinical Rheumatology -