PINK1/Parkin相关线粒体自噬与心血管疾病的研究进展

线粒体是细胞的能量工厂,受损或衰老的线粒体会严重影响细胞生存。线粒体自噬是指细胞通过自噬选择性地清除受损或衰老线粒体的过程,对线粒体质量控制及细胞生存具有重要作用。大量研究表明PINK1/Parkin相关线粒体自噬参与多种疾病的发展过程。现就近年来PINK1/Parkin相关线粒体自噬及线粒体自噬与心血管疾病的研究进展做一综述。     

细胞自噬与心血管疾病中炎症反应的相关性

细胞自噬既是保守的细胞防御机制,也是程序性细胞死亡(即调亡)机制,其可维持细胞自身内环境的稳态。心血管疾病多伴有炎症反应并与细胞自噬密切相关。新近研究表明:一方面,自噬可以通过清除堆积蛋白和保持线粒体稳态对抗心血管疾病的炎症反应,此效应可能与抑制炎症小体以及钙蛋白酶依赖的白介素-1α的活性有关;另一方面,自噬在某些情况下也可促进炎症反应,自噬相关蛋白和高尔基体重组-堆叠蛋白参与了自噬的促炎效应。以本文简要综述细胞自噬在心血管疾病炎症反应中的作用,探讨自噬与炎症反应的相关分子机制,为心血管疾病中炎症反应的治疗提供新的思路。     

自噬在心血管疾病中的作用

自噬是一种维持细胞稳态的重要通路。在特定环境下,细胞中的多余蛋白质和受损细胞器通过自噬这一途径被降解。自噬在多种心血管疾病中的作用正逐渐被阐明,例如缺血/再灌注损伤、动脉粥样硬化、心律失常、高血压和心力衰竭等。本文介绍了影响自噬基本过程的主要分子和调控自噬活性的机制,讨论了自噬与多种心血管疾病之间的关系。     

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。     

自噬与血管衰老的研究进展

<正>自噬是由细胞质起源的自噬体与溶酶体融合降解胞内异常分子和长寿命蛋白的过程,是一种特殊分解代谢途径。它在细胞代谢、存活与分化等方面都具有重要作用。当前社会正朝向老龄化社会演变,关注老龄化相关疾病的研究显得格外重要。随着细胞生物科学与老年医学的相互交叉发展,自噬在老年性心血管疾病、神经退行性疾病、脏器衰老等方面的研究中取得进展。研究已发现通过对自噬调控能够对血管组成细胞的增殖、分化和转归起到重要的调控作用。本文对自噬与血管     

运动对细胞自噬的调控及心血管疾病的影响

自噬是细胞维持自身稳态的重要机制之一,通过溶酶体降解异常蛋白聚积物、清除损伤和老化的细胞器,对保持细胞正常活力与功能具有重要意义。运动是调控细胞自噬的刺激因素之一,单次运动短暂上调细胞自噬活性,促进细胞自我更新;长期运动不仅能提高基础自噬水平,并且对异常的细胞自噬具有调控作用,在心血管疾病防治中发挥有益作用。现主要介绍不同持续时间及不同强度的运动对细胞自噬的诱导作用,以及运动通过调控细胞自噬对心血管疾病的影响。     

巨噬细胞的自噬在动脉粥样硬化中的作用

<正>自噬是细胞依赖于溶酶体进行自我保护的代谢途径。自噬不仅能维持人体正常生理功能,而且在心血管疾病、恶性肿瘤、神经退行性疾病和免疫系统疾病中发挥着重要作用。动脉粥样硬化是血管的慢性炎症反应的过程,炎症反应促进动脉粥样硬化的进展,并贯穿于动脉粥样硬化进展的不同阶段。研究发现~([1])自噬促进胆固醇外流、减少细胞凋亡、干预胞葬作用、并减弱炎症信号从而抑制动脉粥样硬化过程。因此,诱导巨噬细胞自噬将成为治疗动脉粥样硬化的潜     

血管平滑肌细胞自噬与心血管疾病关系及药物干预的研究进展

心血管疾病是危害人们身体健康的常见疾病之一,可损伤心脏及血管功能,血管平滑肌细胞(VSMC)功能在心血管疾病的发生发展过程中发挥着重要作用,而自噬在VSMC的生长、分化过程中发挥着至关重要的作用。本文主要综述了VSMC自噬与心血管疾病关系及药物干预的相关研究进展,以期为心血管疾病发病机制、病理学及新药开发研究提供参考。     

Parkin介导的线粒体自噬:调控心血管疾病的新机制

Parkin是由PARK2基因编码的蛋白,其基因突变和蛋白表达异常首先在帕金森病患者中发现。近年来研究发现Parkin除参与神经、肿瘤疾病的发生发展外,在心血管疾病中也发挥显著作用。研究表明,Parkin通过介导线粒体自噬参与对细胞内受损线粒体的清除,来维持细胞内环境稳态和线粒体正常形态结构。现主要总结了Parkin介导的线粒体自噬的研究现状及其在心血管疾病中的作用及机制,这些发现将为Parkin介导的线粒体自噬与心血管疾病发病机制之间可能存在的联系提供理论依据,并探索新的治疗心血管疾病的靶点。     

自噬与病毒性心肌炎关系研究进展

自噬（autophagy）是细胞依赖溶酶体对胞内蛋白质和受损细胞器进行降解的一条重要途径。细胞自噬受各种因子的精密调节,是细胞清除损伤物质和维持细胞稳态的重要调节方式,与心血管疾病、肿瘤和神经退行性疾病发生密切相关［1］。近几年有文献报道病毒性心肌炎中存在细胞自噬现象［2~4］,结合作者前期试验在小鼠病毒性心肌炎模型中亦观察到细胞自噬现象,因此本文就自噬与病毒性心肌炎的关系进行综述。     

How to Mediate Cardioprotection in Ischemic Hearts—Accumulated Evidence of Basic Research Should Translate to Clinical Medicine

Ischemic heart failure is one of the leading causes of death in the western countries and it is a critical issue to overcome ischemic heart diseases for the human health care worldwide. There are several aspects of ischemic heart failure that we need to seriously consider for the conquest of cardiovascular death. First of all, we need to know either causes or pathophysiology of the onset of coronary artery disease, the ischemia/reperfusion injury and post-infarction cardiac remodeling. Secondly, we need to find the potential seeds for the molecular, pharmacological, biomedical or engineering treatment to prevent or attenuate ischemic heart diseases. Thirdly, we need to accelerate translational research and to create the network of clinical trials to grow the novel seeds to the fruitful big trees. Finally, we need to justify these strategies to overcome the ischemic heart diseases and to contribute the world welfare systems after we propose the novel therapy for the prevention and attenuation of ischemic heart diseases. The most strong and essential hypotheses to attenuate the cardiovascular injury in ischemic heart disease for last three decades are ischemic preconditioning/postconditioning. Many investigators have involved in the clarification of the characteristics of ischemic preconditioning/postconditioning and their cellular mechanisms, and the clinical applications of their basic results. Here, 8 potential basic and clinical researchers includeing us discuss these issues that they have devotedly studies for many years.     

MicroRNA-21在心血管病中的研究

MicroRNA-21(miR-21)在乳腺癌、肝癌、膀胱癌、肠癌等多种癌疾病中被激活有高表达,同样在心血管系统中也有高表达。研究发现：在心脏衰竭、肥厚性心肌病、增殖性血管疾病和缺血性心脏病等心血管疾病中,microRNA-21在心血管中的表达出现下调；microRNA-21对血管平滑肌的增殖和调亡、心肌细胞的生成和死亡、心肌纤维的功能方面有着重要的作用；microRNA-21通过功能的缺失和功能的获得参与心血管疾病发生和发展的病理过程,通过调节多种靶蛋白基因的表达来影响细胞的生长、调亡和细胞的侵润。 MicroRNA-21的调节是依赖于各种转录因子和染色体的复杂程序过程。程序性死亡基因4(Programmed cell death 4 ,PDCD4)、弹力蛋白同源十号染色体缺失的磷酸酶(phosphatase and tensin homology deleted from chromosome 10,PTEN)、出芽蛋白因子1(sprouty1,SPRY1)和出芽蛋白因子2( sprouty2,SPRY2) 是目前被确认的microRNA-21作用靶基因,它们参与miR-21对心血管影响的调节。MicroRNA-21可能成为在心血管疾病中新的治疗靶点。     

MicroRNA-21 in Cardiovascular Disease

MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. miR-21 might be a novel therapeutic target in cardiovascular diseases. This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease.     

Asymmetric dimethylarginine as a marker of metabolic dysfunction and cardiovascular disease

Substantial effort has been devoted to the prevention of cardiovascular diseases through modifiable lifestyle factors, but more innovation is needed to better understand mediators of disease progression and to ultimately improve risk prediction. Markers of endothelial dysfunction and oxidative stress may contribute to the underlying processes of atherosclerosis and premature coronary heart disease. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has emerged as a potential novel marker of cardiovascular disease. Accumulation of ADMA leads to endothelial dysfunction and initiates and promotes processes involved with atherogenesis. Plasma ADMA levels have been associated with coronary heart disease, diabetes, hypertension, stroke, and peripheral arterial disease. ADMA may be an important link between endothelial dysfunction and cardiovascular disease risk and progression. This review discusses the current literature on ADMA as a novel marker of metabolic dysfunction and cardiovascular disease.     

MicroRNAs in Cardiovascular Diseases: Biology and Potential Clinical Applications

Cardiovascular diseases represent one of the major causes for increasing rates of human morbidity and mortality across the world. This reinforces the necessity for the development of novel diagnostics and therapies for the early identification and cure of heart diseases. MicroRNAs are evolutionarily conserved small regulatory non-coding RNAs that regulate the expression of large number of genes. They are involved in several cellular pathophysiological pathways and have been shown to play a significant role in the pathogenesis of many disease states. Recent studies have correlated dysregulated miRNA expressions to diseased hearts and also shown the relevance of miRNA in growth, development, function, and stress responsiveness of the heart. The possibility of exploiting miRNAs to develop diagnostic markers or manipulating them to obtain therapeutic effects is very attractive since they have very specific targets in a particular cellular pathway. In this review we will summarize the role played by miRNAs in the heart and discuss the scope of utilizing miRNA-based strategies in the clinics for the benefit of mankind.     

CYR61在心血管疾病中的研究进展

富含半胱氨酸的血管生成诱导剂61?是结缔组织生长因子家族基质细胞蛋白的成员,参与许多重要生物学功能,具有广泛的生物学特性,在肿瘤性疾病、自身免疫性疾病、肾脏疾病中研究较为广泛,近年来在心血管系统中的研究越来越多,在动脉粥样硬化、心肌损伤、心肌纤维化中具有重要的生物学作用,参与了冠心病、高血压、心力衰竭等心血管疾病的发生发展。CYR61还可作为疾病的标志物,对疾病的治疗提供新的靶点。     

NK细胞与冠心病的关系

冠心病（CHD）是动脉粥样硬化导致器官病变的最常见类型,也是危害人类健康的常见病,近年来研究表明炎症免疫反应与CHD的发生、发展及心梗后的损伤修复密切相关。NK细胞作为先天性免疫系统的重要组成成分,参与了CHD的发生、发展及缺血后的心肌重塑。本文简要概括了NK细胞与CHD的研究进展,以期为CHD的治疗提供新的思路。     

Renal denervation and treatment of hypertension

Cardiovascular diseases kill more people each year than any other diseases. In 2008, 7.3 million people died of ischaemic heart disease, 6.2 million from stroke or another form of cerebrovascular disease. Hypertension affects about 1 billion people worldwide and is a major risk factor for many cardiovascular diseases, including coronary heart disease and stroke. In contrast, our knowledge in regard to the underlying molecular mechanisms remains incomplete and, as a consequence, it is difficult if not impossible to efficiently treat the most affected patients. While the development and application of novel pharmacological agents in combination with lifestyle changes have been applied in Western developed countries to a large number of patients, a significant number of individuals fail to respond. Recently, several novel approaches have been developed including a minimally invasive catheter-based renal nerve ablation technique and some of the consequences will be highlighted in this brief review article. This will include the discussion of previous attempts to denervate the renal arteries as well as the significant improvements achieved when catheter-based interventions are applied.     

颗粒酶B在心血管疾病中的重要作用

细胞凋亡在心血管疾病如动脉粥样硬化,缺血性心脏病,充血性心力衰竭中起着重要的作用。以往的研究已经证明氧化应激、生理应激、肿瘤坏死因子和Fas配体参与了心血管系统的细胞凋亡。而最近的研究证明了另一个凋亡相关因子,即颗粒酶B/穿孔蛋白系统也参与了心血管系统的细胞凋亡。在这篇综述中,我们阐述了颗粒酶B在心血管疾病中的作用,并且发现颗粒酶B抑制剂的实验应用可以减轻心血管病的发生发展,从而使抑制颗粒酶B/穿孔蛋白系统治疗心血管疾病成为可能。