线粒体动力学、线粒体自噬和心血管疾病

线粒体是一种动态的细胞器,通过响应各种代谢和环境的信号, 分裂和融合改变其形态和结构,从而维持细胞的正常功能。它们短暂而快速的形态变化对于细胞周期、免疫、凋亡和线粒体自噬的质量控制等许多复杂的细胞过程至关重要。线粒体自噬与线粒体质量控制密切相关,通过将受损的功能障碍的线粒体转运到溶酶体进行降解,促进心肌细胞受损线粒体的更新,并有效地抑制功能障碍线粒体的积累。由于心脏作为一个复杂而高耗能的器官,心肌细胞严重地依赖线粒体氧化代谢过程作为其能量和营养供应的来源。许多研究表明,线粒体融合、分裂和线粒体自噬的诸多影响和调控功能的因子都与各种心血管疾病有关,维持线粒体的功能和其完整性对正常心肌细胞的运行是至关重要的。在这篇的综述中,我们将重点概述一下线粒体的融合、分裂和线粒体自噬的诸多调控因子与心血管疾病的最新研究进展。     

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的细胞（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。     

血管内皮细胞线粒体动力学相关功能与心血管疾病关系的研究进展

细胞线粒体动力学相关功能是指线粒体通过不断地融合与分裂、线粒体自噬及线粒体-内质网结构偶联来维持细胞正常生理功能的过程。其异常与神经退行性病变、肿瘤、视神经萎缩及糖尿病等疾病的发生发展关系密切。近年来,血管内皮细胞（vascular endothelial cell,VEC）线粒体相关功能在心血管疾病中的研究受到广泛关注,研究发现VEC线粒体相关功能异常在心肌缺血/再灌注（I/R）损伤、冠状动脉粥样硬化、肺动脉高压及扩张型心肌病等疾病的发生发展中发挥重要作用。本文就VEC线粒体动力学相关功能及与心血管疾病的关系进行简要阐述。     

线粒体自噬在COPD发病机制中作用的研究进展

慢性阻塞性肺疾病(COPD)是最常见的呼吸系统疾病之一.自噬是内质网膜包裹并降解异常蛋白质和细胞器的细胞途径,对维持细胞正常生理功能至关重要.线粒体是细胞中最重要的细胞器,主要参与能量生成和氧化还原反应等重要细胞过程.线粒体自噬是一种选择性清除损伤线粒体的自噬过程,是维持线粒体功能和数量正常的重要途径.越来越多的研究发现,线粒体自噬在COPD的病理生理过程中发挥着重要作用,故本文将线粒体自噬在COPD发病机制中的作用进行综述.     

线粒体融合蛋白2在心血管疾病中的研究现状

线粒体是一个处于不断地融合与分裂过程中的动态细胞器。线粒体融合蛋白2(Mfn2)作为广泛分布于线粒体外膜和线粒体结合内质网膜上具有多重功能的蛋白,参与维持正常细胞功能。除了参与线粒体融合外,Mfn2还能够调节线粒体代谢、促进损伤线粒体的自噬、增强线粒体与内质网交流、维持内质网功能及通过调控线粒体外膜通透性和渗透性钙转运孔道的启闭参与细胞死亡过程等。另外,Mfn2基因还可通过调控Ras-Raf-ERK/MAPK和Ras-PI3K-Akt信号通路分别参与调控血管平滑肌细胞的增殖和凋亡过程。Mfn2的这一系列重要的生物学功能有助于其参与高血压、肺动脉高压、动脉粥样硬化、急性缺血/再灌损伤、扩张性心肌病、心肌肥大、心衰和肥胖糖尿病等多种心血管疾病的发生发展过程。研究Mfn2与心血管疾病的相关性也许能为临床提供一个心血管疾病潜在治疗的靶点。因此,本文将综述Mfn2在心血管疾病相关研究中的现状。     

线粒体质量控制与心血管疾病

心肌线粒体是心脏能量代谢的主要部位,其功能障碍可导致多种心血管疾病.线粒体质量控制主要通过调控线粒体的生物发生、融合、分裂和自噬,以保证线粒体形态、数量和质量的相对稳定,以维持其结构和功能的完整性.线粒体的质量控制体系在缺血性心脏病、糖尿病性心肌病、心力衰竭、动脉粥样硬化和高血压中发挥重要作用.     

自噬与心肌衰老及心血管疾病关系的研究进展

真核细胞降解细胞内物质主要通过2条途径--蛋白酶体降解和自噬(autophagy)降解[1].蛋白酶体主要降解细胞内短寿命蛋白质;细胞内几乎全部的长寿蛋白质、多数大分子物质以及所有的细胞器都通过自噬作用被运输到溶酶体内降解,以实现细胞本身的代谢需要和细胞器的更新.     

线粒体功能障碍在心血管疾病中的作用

心血管疾病(CVD)在世界范围内分布广泛,是导致人类死亡的主要原因之一。CVD有着复杂的病因,多种危险因素和病理机制可导致CVD。在细胞中,代谢异常、活性氧的过量产生、能量供应不足、自噬功能障碍、内质网应激和凋亡的激活等各种异常均可导致线粒体功能障碍。最近研究表明线粒体功能障碍在CVD的发生和发展中起着关键作用。现强调心肌细胞内线粒体功能障碍在CVD中的相关作用机制,为找到疾病新的治疗靶点带来启发。     

线粒体功能障碍与血管内皮损伤的研究进展

线粒体功能障碍会导致ATP的生成减少,活性氧的产生增加,被认为是血管内皮损伤的触发因素之一。许多因素与线粒体功能障碍有关,如线粒体DNA突变、线粒体融合与分裂失衡、线粒体自噬受损等。本文综述了线粒体的质量控制过程和线粒体功能障碍在血管内皮损伤中的作用机制,以期为动脉粥样硬化的有效防治提供新的思路。     

主动脉根部内径与心血管疾病的关系

目的 分析北京社区中老年人群主动脉根部内径与心血管疾病危险因素及心血管疾病的关系.方法 2004至2005年在北京首钢地区对1061名居民进行流行病学调查,选取超声心动资料齐全者共1041名进行分析.采用超声心动图测量主动脉根部内径、左心室质量、室间隔和左心室后壁厚度以及左心室大小,同时调查相关心血管危险因素及心血管疾病.采用spearman相关计算主动脉根部内径与其他心血管危险因素的关系.采用多因素logistic回归计算主动脉根部内径与心血管疾病的关系.结果 近端升主动脉内径(AAD)和平均根部内径(MRD)与年龄、体重、体质指数(BMI)、收缩压和舒张压相关(P<0.01),还与左心房大小、左心室质量、室间隔及左心室后壁厚度,左心室大小相关(P<0.01).以AAD和MRD下四分之一位数为参考,女性AAD上四分之一位数卒中、心力衰竭、总体心血管疾病OR值分别为2.20(95%CI:1.03~4.72,P=0.04),2.62(95%CI:1.49~4.61,P=0.001),2.52(95%CI:1.51,4.21,P<0.001);MRD上四分之一位数心力衰竭、总体心血管疾病的OR值分别为2.19(95%CI:1.26~3.80,P=0.01),2.20(95%CI:1.32~3.68,P=0.002).调整年龄、BMI、吸烟史、总胆固醇、高血压和糖尿病后,上述结果不再具有统计学意义(P>0.05).结论 主动脉根部内径相关指标与某些心血管疾病危险因素相关,但不与心血管疾病独立相关,可能是心血管疾病的一个中间指标.联合主动脉根部内径及传统的心血管疾病危险因素或许可以更好地评估心血管疾病.

Abstract：

Objective To analyze the relation among aortic root dimension(ARD) measured by echocardiography, cardiovascular disease risk factors and cardiovascular disease in adult Beijing community population.Methods Echocardiography was performed in 1041 individuals in a suburban community of Beijing from 2004 to 2005. ARD and other echocardiographic parameters including left atria dimension, left ventricular mass, septal and posterior wall thickness and dimension were analyzed. Histories of cardiovascular disease as well as risk factors were obtained. Spearman correlation was used to determine the relation between ARD and other cardiovascular risk factors. Multifactorial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ARD and cardiovascular disease.ResultsAscending aortic dimension (AAD) and mean root dimension(MRD) were positively associated with age, weight, BMI, systolic and diastolic blood pressure, left atria dimension, left ventricular mass, left ventricular septal and posterior wall thickness, and left ventricular dimension. With the lowest quintile of AAD and MRD as the reference, ORs for the highest quintile of AAD for specific cardiovascular diseases in female were as follows: stroke (OR=2.20,95%CI:1.03-4.72,P=0.04),chronic heart failure (OR=2.62, 95%CI:1.49-4.61,P=0.001),total cardiovascular disease (OR=2.52, 95%CI:1.51-4.21,P<0.001).ORs of MRD were as follows: chronic heart failure (OR=2.19, 95%CI:1.26-3.80,P=0.01), total cardiovascular disease (OR=2.20, 95%CI:1.32-3.68,P=0.002). After adjustment for age, BMI, smoking status, TC,hypertension, diabetes mellitus, the ORs were not statistically significant (P>0.05).Conclusion ARD was positively associated with several CHD risk factors, but was not independent risk factor for cardiovascular disease. ARD may act as an intermediate risk factor for cardiovascular disease. Combined ARD and traditional cardiovascular disease risk factors might enhance the predict power for cardiovascular disease.     

回顾性调查线粒体疾病患者的心脏病变

目的 分析线粒体疾病心脏受累的表现,提高对该病的认识.方法 回顾北京协和医院20年来诊断的90例线粒体疾病患者临床与病理资料,包括心电图、动态心电图和心脏超声检查.结果 90例线粒体疾病患者中合并心脏病变29例.其中合并心肌病变5例(5.6%),为左心室肥厚2例、心脏扩大伴心力衰竭3例;合并先天性结构性心脏病4例(4.4%),包括三尖瓣或(和)二尖瓣脱垂各1例,房间隔或室间隔缺损各1例;各种不同程度心律失常20例(22.2%),包括安装永久起搏器者4例(3例在安装起搏器后1～3年才诊断为线粒体疾病),多种心律失常包括室性心动过速1例,阵发性房性心动过速1例,无症状的心律失常14例(分别是右束支传导阻滞4例,右束支合并左前分支传导阻滞1例,短PR间期综合征5例,B型预激综合征2例,室内传导阻滞2例).心脏传导阻滞在Kearns-Sayre综合征(9例)中发生率高达66.7%.8例患者检出线粒体基因A3243G突变.结论 线粒体疾病可以心肌病、心力衰竭、恶性心律失常为首发表现,对青壮年心肌病、伴发严重的心脏传导阻滞应尽可能寻找病因包括进行相关基因检查.此外,对所有诊断为线粒体疾病患者需定期进行心电图和超声心动图等检查以便尽早发现异常及早处理以改善预后.     

尼克酰胺腺嘌呤二核苷酸磷酸氧化酶与心血管疾病关系的研究进展

活性氧的增加与心血管疾病密切相关,而产生活性氧的主要酶体是尼克酰胺腺嘌呤二核苷酸氧化酶(NADPH氧化酶)。NADPH氧化酶对动脉粥样硬化、高血压、心力衰竭的发生发展起着重要的作用;而心房颤动又可引起NADPH氧化酶的增加。     

Relation of aging and sex hormones to metabolic syndrome and cardiovascular disease

Several factors such as age, gender, race, lifestyle and diet, contribute to the prevalence of the metabolic syndrome, which has become the new epidemic of this century. They also contribute to the prevalence, age of appearance and outcome of cardiovascular disease, which is the number one cause of morbidity and mortality in men and women worldwide. Metabolic syndrome increases the risk of developing cardiovascular diseases, hypertension and type-2 diabetes, among other diseases. In this paper we analyze from a pathogenetic point of view, two of the factors which contribute to the increasing prevalence of the metabolic syndrome and cardiovascular diseases: age and gender. The gender variations are a consequence of the different rate of decrease of sexual hormones in males and females and of the protective roles they play during adulthood and older age phases.     

勃起功能障碍与心血管疾病

近来发现 ,勃起功能障碍与心血管疾病关系密切。在发病机制上 ,二者呈鲜明的共因和互为因果关系 ;在治疗上 ,二者之间的相互影响十分显著     

Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well-designed intervention studies, randomized clinical trials and long-term follow-up studies are scarce.     

他汀类药物治疗心血管疾病研究进展

血脂异常是致动脉粥样硬化的主要因素,动脉粥样硬化是心血管疾病的重要基本病变,在此基础上的动脉内血栓形成是急性心血管事件的首要原因。他汀类药物调节血脂和减少血栓形成可以减少心血管疾病的发生。     

心血管疾病临床诊断与尸检病理分析

目的 探讨心血管疾病死亡或其他疾病并发心脏损害的患者临床尸检结果.方法 对86例死亡原因不确定的患者进行完整尸体解剖,结合临床诊治经过、尸检肉眼所见及镜下观察结果,确定引发死亡的主要病因.结果 86例尸检中有心脏病变69例.比较病理诊断和临床诊断的差异,心源性死亡患者27例,诊断相符率为81.5%;非心脏性疾病但并发或累及心脏并加速患者死亡42例,诊断相符率为78.6%.结论 科学准确地进行尸体解剖,不但可明确死因,而且丰富和发展相关临床学科的内容,对提高诊治水平具有重要意义.

Abstract：

Objective To investigate the clinical autopsy results of patients died of cardiovascular disease or other disease complicated with cardiac damage. Methods Complete autopsy was performed on 86 cases with uncertain cause of death. Through integrating clinical diagnosis and treatment with gross autopsy findings and microscopic observations, 86 autopsies were determined the major cause of death. Results In 86 autopsies, 69 cases were heart disease. Differences between pathological diagnosis and clinical diagnosis were compared. Twenty-seven cases were cardiac deaths, with diagnosis accrodance rate of 81. 5%. Fortytwo cases died of non-cardiac disease but complicated with heart disease or involving the heart which accelerated the death in patients, with accordance rate of 78.6%. Conclusion Scientific and correct performance of autopsy was important to determine the causes of death, to promote development of related disciplines and to improve the diagnosis and treatment of the diseases.