线粒体动力学和线粒体自噬与心血管疾病的研究进展

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...     

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。     

Neural and humoral mechanisms mediating cardiovascular responses to obstructive sleep apnea

Patients with obstructive sleep apnea are at increased risk for hypertension. The mechanisms underlying this increased risk are not known. During sleep, repetitive apneic episodes result in hypoxemia and carbon dioxide retention, which cause increases in sympathetic nerve activity and elicit humoral vasoconstrictor responses. While these mechanisms explain nocturnal elevations in blood pressure, it is unclear why hypertension and elevated sympathetic nerve activity prevail even during the daytime. This review will examine briefly some of the neural and humoral mechanisms that are activated by nocturnal apneas and which may contribute to persistent increases in blood pressure even during daytime normoxia. Disruption of the autonomic and hemodynamic profile of normal sleep by apneic events manifests as raised blood pressure and heightened sympathetic nerve traffic during sleep. During awake daytime normoxia, baroreflex and chemoreflex dysfunction may contribute to maintenance of higher blood pressure and sympathetic activity. Sustained vasoconstrictor effects of nocturnal endothelin release may also be implicated in the elevated daytime blood pressures.     

Mineralocorticoid receptors and pathophysiological roles for aldosterone in the cardiovascular system

For almost 40 years since its discovery in 1953, the mineralocorticoid hormone, aldosterone, was considered to affect blood volume, and thus blood pressure, by its action to retain sodium at epithelial tissues. Over the past decade, direct effects of aldosterone on the heart and blood vessels, and on the cerebral control of blood pressure, have been established in experimental animals. Simultaneously, the incidence of primary aldosteronism in essential hypertension is now acknowledged to be 10-20%, rather than 相似文献   

miR-34a在心血管疾病中的作用及机制研究进展

微小RNA(miR)是心血管疾病发生发展的重要调控因子。其中,miR-34a因广泛参与心血管疾病的病理生理过程成为目前研究热点。在冠状动脉粥样硬化性心脏病等心血管疾病中均存在miR-34a的异常表达。本文就miR-34a对心血管疾病的作用及其机制研究进展进行综述,为寻求心血管疾病标志物及治疗靶点提供新思路。     

线粒体损伤在肝功能衰竭发生中的分子机制

肝功能衰竭是由多种因素引起的,以肝细胞大量凋亡、坏死为特征的临床综合征.其病情危重,发展迅速,病死率高达60％～80％.线粒体是真核细胞中一种非常重要的细胞器,与肝脏的生物合成、代谢和解毒功能密不可分.三羧酸循环、脂肪酸β-氧化、氧化磷酸化及鸟氨酸循环等均在线粒体内进行.此外,线粒体在调节细胞内钙离子浓度、信息传递及细胞死亡等过程中也具有重要作用.线粒体是肝细胞内较敏感的细胞器之一,多种急、慢性肝病均存在线粒体结构和功能的异常.有研究结果显示,线粒体与肝衰竭的发病关系密切,可能的作用途径包括:呼吸链被抑制导致三磷酸腺苷(adenosine-triphosphate,ATP)耗竭、氧化应激、脂肪酸β-氧化的抑制、线粒体通透性转换(mitochondrial permeability transition,MPT)所致肝细胞凋亡或坏死等,但其作用机制尚未完全阐明[1].现就目前的相关研究进展作一综述.     

膜联蛋白A3在心血管系统中的作用

膜联蛋白(ANX)是一类进化过程中高度保守的细胞内蛋白质,其名字最初来源于希腊语“annexin”,意为“结合在一起”。ANX通常以钙离子浓度依赖的方式与细胞膜磷脂结合,发挥胞吞、胞吐、转运、信号传递等功能。膜联蛋白A3(ANXA3)是ANX家族中重要的成员之一,大量研究发现其与肿瘤的演进有密不可分的关系。近些年,随着生物信息学技术的不断发展,越来越多的研究表明,ANXA3在心血管系统中也发挥着不可小觑的作用。深入揭示ANXA3在心血管系统中的作用,未来可望能够为心血管损伤相关疾病的防治提供新的思路与策略。     

The effects and mechanisms of thyroid hormones in the cardiovascular system

Background Thyroid hormones(THs) including thyroxine(T4) and triiodothyronine(T3) with high biological activities have important effects on cardiovascular system by acting on renin-angiotensin-aldosterone system(RAAS), oxidative stress, mitochondria, endothelial cells, vascular smooth muscle cells(VSMC), cardiomyocytes, thyroid hormone receptor(TRs), cholesterol metabolism, insulin sensitivity, blood coagulation, etc. Excess or lack of THs is detrimental to cardiovascular function, so this article reviews the mechanism of THs on cardiovascular system.[S Chin J Cardiol 2019;20(4):269-279]     

Protein kinase d in the cardiovascular system: emerging roles in health and disease

The protein kinase D (PKD) family is a recent addition to the calcium/calmodulin-dependent protein kinase group of serine/threonine kinases, within the protein kinase complement of the mammalian genome. Relative to their alphabetically superior cousins in the AGC group of kinases, namely the various isoforms of protein kinase A, protein kinase B/Akt, and protein kinase C, PKD family members have to date received limited attention from cardiovascular investigators. Nevertheless, increasing evidence now points toward important roles for PKD-mediated signaling pathways in the cardiovascular system, particularly in the regulation of myocardial contraction, hypertrophy and remodeling. This review provides a primer on PKD signaling, using information gained from studies in multiple cell types, and discusses recent data that suggest novel functions for PKD-mediated pathways in the heart and the circulation.     

Molecular control of nitric oxide synthases in the cardiovascular system

Nitric oxide plays an important role in cardiovascular homeostasis. In this review, the regulation of the three nitric oxide synthase isoforms in the cardiovascular system are examined at molecular and cellular levels. In addition, recent information gleaned from the use of NOS knockout mice are discussed.     

高龄老年患者动脉及心脏结构与功能变化

目的评价高龄老年患者动脉及心脏结构、功能变化。方法老年高血压或糖尿病患者分为两组,高龄组：80岁及以上,119例;老年组：60—79岁,78例。分别检测颈动脉内膜中层厚度（IMT）、冠状动脉钙化积分（CS）、动脉脉压（PP）;心脏超声检测室间隔厚度（IVS）、左室室壁厚度（LVPW）、舒张末期左心室内径（LVDd）、收缩末期左心室内径（LVDs）、收缩末期左心房前后径（LAD）、左室质量（LVM）、左室质量指数（LVMI）、左室射血分数（EF）、左心室舒张早期二尖瓣最大血流速度E峰及舒张晚期二尖瓣最大血流速度A峰比值（E／A）。结果高龄组冠脉钙化总积分（TCS）、右冠脉钙化积分（CSRCA）、IMT、PP、LVPW较老年组增高（P〈0．01）,E／A较老年组下降（P〈0．05）。结论老年期随增龄颈动脉内膜增生及左室肥厚进一步加重;高龄老人心脏舒张功能明湿下降,但对收缩功能影响不大;增龄导致的冠状动脉钙化更易侵犯右冠脉。     

Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction

Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO.) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO. was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography -based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H2O2 production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or glibenclamide. Depletion of p22(phox) subunit of NADPH oxidase with small interfering RNA also inhibited Ang II-mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione, increased state 4 and decreased state 3 respirations, and diminished mitochondrial respiratory control ratio. These responses were attenuated by apocynin, 5-hydroxydecanoate, and glibenclamide. In addition, 5-hydroxydecanoate prevented the Ang II-induced decrease in endothelial NO. and mitochondrial membrane potential. Therefore, Ang II induces mitochondrial dysfunction via a protein kinase C-dependent pathway by activating the endothelial cell NADPH oxidase and formation of peroxynitrite. Furthermore, mitochondrial dysfunction in response to Ang II modulates endothelial NO. and generation, which in turn has ramifications for development of endothelial dysfunction.