线粒体功能障碍与高血压

高血压发病率在全球范围内呈逐年上升趋势,全面深入研究高血压发病机制已成为医学界共识。与线粒体功能障碍有关的供能不足、氧化损伤、信号传导异常和线粒体基因突变是高血压产生的危险因素。了解线粒体功能损伤与高血压的关系将为高血压的研究和治疗提供新的思路。本文从线粒体功能、线粒体功能障碍以及线粒体功能障碍与高血压的关系三个角度做详细阐述。     

线粒体功能障碍在心肌缺血再灌注损伤发病中的作用及靶向治疗研究进展

心肌缺血再灌注时,心肌线粒体的结构和功能受到多种因素的影响导致线粒体功能障碍,可引起线粒体ATP生成减少、Ca2+超载、活性氧暴涨、线粒体跨膜电位降低以及膜通透性提高,这些因素最终会导致线粒体过度自噬以及内源性细胞凋亡和坏死,心肌细胞死亡数目急剧上升,出现心肌缺血再灌注损伤(MIRI)。通过对MIRI患者线粒体功能障碍的靶向治疗,给予尼克地尔、雷帕霉素等靶向药物,抑制线粒体功能障碍引起的不良事件,可减轻线粒体损伤,从而改善心肌细胞活力和减轻MIRI。     

线粒体损伤及其在心肌细胞损伤中的作用

<正>重度失血、严重缺氧或酸中毒及脓毒血症均可引起心脏能量代谢障碍,使循环功能急剧减退,组织器官微循环灌流严重不足,导致重要生命器官功能、代谢严重障碍,严重影响治疗及预后,成为危重患者死亡的重要原因之一~(〔1〕)。线粒体损伤已成为心肌细胞结构损伤与功能障碍的基本环节~(〔2〕)。关于线粒体在多种致病因素导致心肌细胞损伤与功能障碍中的作用,目前认为与呼吸链酶类变化、一氧化氮(NO)释放、钙超载、线粒体     

血管内皮功能障碍与高血压

血管内皮功能障碍与高血压密切相关。一方面血管内皮功能障碍在高血压的发生、发展过程中起重要作用;另一方面高血压本身又加重血管内皮功能障碍,形成恶性循环。现综述血管内皮细胞的生理功能、血管内皮功能障碍的相关因素、血管内皮功能障碍与高血压关系、血管内皮功能检测及血管内皮功能障碍的修复等方面的研究进展。     

微小RNA对缺血再灌注损伤心肌线粒体作用的研究进展

心肌缺血再灌注损伤是造成心肌结构损伤、功能障碍的一种病理生理过程,进一步发展会导致级联的多器官功能障碍。线粒体是一种结构功能复杂且对外界环境反应敏感的细胞器,其稳态的维持依赖于正常形态、功能及数量的相对稳定状态。线粒体质量与代谢异常和心血管疾病尤其是心肌缺血再灌注损伤的发生密切相关。微小RNA是近年来研究较多的在缺血再灌注损伤心肌线粒体保护中具有重要作用的调控因子。本文通过微小RNA对心肌缺血再灌注损伤时线粒体形态、功能、线粒体自噬和线粒体DNA几个方面的调控机制与相关前沿进展进行综述,为微小RNA参与缺血再灌注心肌线粒体损伤的后续研究提供一定的理论依据。     

线粒体移植在心肌缺血再灌注损伤中的作用

线粒体移植是可改善线粒体功能障碍导致的心肌损伤、维持心脏稳态的新兴技术.该文总结了线粒体移植产生心肌保护的作用机制,介绍了线粒体内化、来源、移植方法以及线粒体移植在心肌缺血再灌注损伤中的应用.线粒体移植为心肌缺血再灌注损伤的临床治疗提供了新思路.     

线粒体功能障碍与年龄相关性黄斑变性研究进展

<正>线粒体在不同的细胞中密度不同,在代谢活跃的细胞如视网膜色素上皮细胞中大量表达。氧化性损伤导致的线粒体功能障碍已经成为衰老性疾病的发病机制之一〔1〕。越来越多的证据表明线粒体功能障碍与视网膜疾病之间存在联系。1线粒体是细胞功能和代谢方面起重要作用的细胞器它的主要作用是产生腺苷三磷酸,控制细胞代谢和调节细胞凋亡,线粒体内膜和外膜由磷脂双分子层组成,含有大量的镶嵌蛋白。线粒体基因组不稳定性是年龄相关性疾病的促成因素。由氧化性应激导致的线粒体功能障碍在年龄相关性黄     

非线粒体辅酶Q10在线粒体损伤所致心血管疾病中治疗机制研究进展

线粒体损伤与心血管疾病(CVD)的发生密切相关,减少线粒体损伤能够显著减少心血管事件发生。近年研究发现,非线粒体辅酶Q10(CoQ10)对防治线粒体损伤所致CVD具有一定作用,其机制可能与降低内皮型一氧化氮合酶解耦联状态以及活性氧积聚等作用来减少线粒体结构和功能损伤有关。因此,非线粒体Co Q10在线粒体损伤所致CVD治疗方面有良好的开发利用前景,值得引起重视。     

中医药保护动脉粥样硬化血管内皮功能研究进展

血管内皮损伤与动脉粥样硬化的发病机制密切相关,内皮功能障碍不仅是动脉粥样硬化的始动因素。中医药具有保护血管内皮功能,减轻动脉粥样硬化的作用。本文主要从单味中药、中药复方种类及作用机制等方面进行概述,总结近年中医药保护动脉粥样硬化血管内皮功能的最新研究进展,为深入研究提供参考。     

线粒体损伤与心血管疾病关系的研究进展

线粒体通过其产生能量而被视为细胞的动力源,近年在心血管疾病中的作用日益受到关注.线粒体被认为是活性氧产生、炎症、新陈代谢和细胞死亡的关键调节剂.现有证据表明线粒体DNA(mtDNA)损伤可导致线粒体功能障碍继而导致心血管疾病发生.本文对有关线粒体损伤与心血管疾病关系的新进展作一综述.     

线粒体及其蛋白质质量控制失调与动脉粥样硬化的关系

线粒体是哺乳动物细胞内重要的细胞器,作为细胞能量代谢和细胞死亡的调控中心,其功能异常会导致多种疾病的发生与发展。 线粒体功能依赖于线粒体蛋白质组的完整性和稳态,因此线粒体蛋白质质量控制系统对于维持线粒体稳态和机体健康十分重要。当线粒体及其蛋白质质量控制系统出现异常时,会直接损伤线粒体并出现异常线粒体蛋白堆积,发生细胞内环境紊乱,甚至细胞功能障碍,进而影响动脉粥样硬化性疾病的发生与发展。文章回顾了线粒体及其蛋白质质量控制系统在动脉粥样硬化性疾病发生发展中的作用,并对该领域未来的发展前景和挑战进行展望,以期为寻找与动脉粥样硬化性疾病密切相关的特异性线粒体蛋白提供线索。     

Direct cytotoxicity of hypoxia-reoxygenation towards sinusoidal endothelial cells in the rat

Abstract: Aims/Background: Sinusoidal endothelial cells are the primary target of ischemia-reperfusion injury following liver preservation. The present study was undertaken to examine the susceptibility of sinusoidal endothelial cells to hypoxia-reoxygenation and the potential role of oxygen free radicals in the induction of cell injury. Methods: Sinusoidal endothelial cells were isolated from rat liver. After 2–3 days of primary culture, the cells were exposed to hypoxia (N₂/CO₂ 95/5) for 120 min and reoxygenation (O₂/CO₂ 95/5) for 90 min. Control cells were exposed to hypoxia alone, to 95% O₂ alone or were maintained under normoxic conditions. Human umbilical vein endothelial cells were used as a model of vascular endothelial cells and submitted to the same protocol. Cell viability and lipid peroxidation were assessed by LDH leakage and malondialdehyde production, respectively. In order to test the potential role of xanthine oxidase and mitochondria dysfunction in cell injury, the cells were treated with allopurinol and potassium cyanide (KCN) respectively. Results: The different gaseous treatments did not affect LDH leakage in human umbilical vein endothelial cells. In sinusoidal endothelial cells, the sequential hypoxia-reoxygenation caused a significant increase in LDH release, malondialdehyde production and xanthine oxidase activity while hypoxia alone had no effect except on xanthine oxidase activity. Allopurinol inhibited xanthine oxidase without preventing cell injury or lipid peroxidation in this latter cell type. Conclusions: The results suggest that sinusoidal endothelial cells, as opposed to vascular endothelial cells, are susceptible to a direct cytotoxic effect of hypoxia-reoxygenation. This effect occurs in combination with an increase in xanthine oxidase activity and lipid peroxidation, although cell injury is mediated at least in part by mechanisms independent of xanthine oxidase such as mitochondrial dysfunction.     

Dynamin‐related protein 1‐mediated mitochondrial fission contributes to post‐traumatic cardiac dysfunction in rats and the protective effect of melatonin

Mechanical trauma (MT ) causes myocardial injury and cardiac dysfunction. However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post‐traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to 5‐minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model. Melatonin was administrated intraperitoneally 5 minute after MT . Mitochondrial morphology, myocardial injury, and cardiac function were determined in vivo. There was smaller size of mitochondria and increased number of mitochondria per μm² in the hearts after MT when the secondary myocardial injury was induced. Melatonin treatment at the dose of 30 mg/kg reduced serine 616 phosphorylation of Drp1 and inhibited mitochondrial Drp1 translocation and mitochondrial fission in the hearts of rats subjected to MT , which contributed to the reduction of myocardial injury and the improvement of cardiac function. In vitro, H9c2 cells cultured in 20% traumatic plasma (TP ) for 12 hour showed enhanced mitochondrial fission, mitochondrial membrane potential (?Ψm) loss, mitochondrial cytochrome c release, and decreased mitochondrial complex I‐IV activities. Pretreatment with melatonin (100 μmol/L) efficiently inhibited TP ‐induced mitochondrial fission, ?Ψm loss, cytochrome c release, and improved mitochondrial function. Melatonin's protective effects were attributed to its role in suppressing plasma TNF ‐α overproduction, which was responsible for Drp1‐mediated mitochondrial fission. Taken together, our results demonstrate for the first time that abnormal mitochondrial dynamics is involved in post‐traumatic cardiac dysfunction. Melatonin has significant pharmacological potential in protecting against MT ‐induced cardiac dysfunction by preventing excessive mitochondrial fission.     

Melatonin,cardiolipin and mitochondrial bioenergetics in health and disease

Abstract: Melatonin is a natural occurring compound with well‐known antioxidant properties. Melatonin is ubiquitously distributed and because of its small size and amphiphilic nature, it is able to reach easily all cellular and subcellular compartments. The highest intracellular melatonin concentrations are found in mitochondria, raising the possibility of functional significance for this targeting with involvement in situ in mitochondrial activities. Mitochondria, the powerhouse of the cell, are considered to be the most important cellular organelles to contribute to degenerative processes mainly through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage to mitochondrial proteins, lipids and DNA. Therefore, protecting mitochondria from oxidative damage could be an effective therapeutic strategy against cellular degenerative processes. Many of the beneficial effects of melatonin administration may depend on its effect on mitochondrial physiology. Cardiolipin, a phospholipid located at the level of inner mitochondrial membrane is known to be intimately involved in several mitochondrial bioenergetic processes as well as in mitochondrial‐dependent steps of apoptosis. Alterations to cardiolipin structure, content and acyl chain composition have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological situations and aging. Recently, melatonin was reported to protect the mitochondria from oxidative damage by preventing cardiolipin oxidation and this may explain, at least in part, the beneficial effect of this molecule in mitochondrial physiopathology. In this review, we discuss the role of melatonin in preventing mitochondrial dysfunction and disease.     

Mitochondrial regulatory mechanisms in spinal cord injury: A narrative review

Spinal cord injury is a severe central nervous system injury that results in the permanent loss of motor, sensory, and autonomic functions below the level of injury with limited recovery. The pathological process of spinal cord injury includes primary and secondary injuries, characterized by a progressive cascade. Secondary injury impairs the ability of the mitochondria to maintain homeostasis and leads to calcium overload, excitotoxicity, and oxidative stress, further exacerbating the injury. The defective mitochondrial function observed in these pathologies accelerates neuronal cell death and inhibits regeneration. Treatment of spinal cord injury by preserving mitochondrial biological function is a promising, although still underexplored, therapeutic strategy. This review aimed to explore mitochondrial-based therapeutic advances after spinal cord injury. Specifically, it briefly describes the characteristics of spinal cord injury. It then broadly discusses the drugs used to protect the mitochondria (e.g., cyclosporine A, acetyl-L-carnitine, and alpha-tocopherol), phenomena associated with mitochondrial damage processes (e.g., mitophagy, ferroptosis, and cuproptosis), mitochondrial transplantation for nerve cell regeneration, and innovative mitochondrial combined protection therapy.     

Mitochondria in vascular disease

Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, the regulation of calcium, and activation of cell death. Mitochondrial dysfunction is part of both normal and premature ageing, but can contribute to inflammation, cell senescence, and apoptosis. Cardiovascular disease, and in particular atherosclerosis, is characterized by DNA damage, inflammation, cell senescence, and apoptosis. Increasing evidence indicates that mitochondrial damage and dysfunction also occur in atherosclerosis and may contribute to the multiple pathological processes underlying the disease. This review summarizes the normal role of mitochondria, the causes and consequences of mitochondrial dysfunction, and the evidence for mitochondrial damage and dysfunction in vascular disease. Finally, we highlight areas of mitochondrial biology that may have therapeutic targets in vascular disease.     

PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function

Oxidative stress is caused by an imbalance between reactive oxygen species (ROS) production and the ability of an organism to eliminate these toxic intermediates. Mutations in PTEN-inducible kinase 1 (PINK1) link mitochondrial dysfunction, increased sensitivity to ROS, and apoptosis in Parkinson's disease. Whereas PINK1 has been linked to the regulation of oxidative stress, the exact mechanism by which this occurs has remained elusive. Oxidative stress with associated mitochondrial dysfunction leads to cardiac dysfunction and heart failure (HF). We hypothesized that loss of PINK1 in the heart would have deleterious consequences on mitochondrial function. Here, we observed that PINK1 protein levels are markedly reduced in end-stage human HF. We also report that PINK1 localizes exclusively to the mitochondria. PINK1(-/-) mice develop left ventricular dysfunction and evidence of pathological cardiac hypertrophy as early as 2 mo of age. Of note, PINK1(-/-) mice have greater levels of oxidative stress and impaired mitochondrial function. There were also higher degrees of fibrosis, cardiomyocyte apoptosis, and a reciprocal reduction in capillary density associated with this baseline cardiac phenotype. Collectively, our in vivo data demonstrate that PINK1 activity is crucial for postnatal myocardial development, through its role in maintaining mitochondrial function, and redox homeostasis in cardiomyocytes. In conclusion, PINK1 possesses a distinct, nonredundant function in the surveillance and maintenance of cardiac tissue homeostasis.     

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。     

Mitochondrial dysfunction in atherosclerosis

Increased production of reactive oxygen species in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are associated with atherosclerosis or cardiomyopathy in human investigations and animal models of oxidative stress. Moreover, major precursors of atherosclerosis-hypercholesterolemia, hyperglycemia, hypertriglyceridemia, and even the process of aging-all induce mitochondrial dysfunction. Chronic overproduction of mitochondrial reactive oxygen species leads to destruction of pancreatic beta-cells, increased oxidation of low-density lipoprotein and dysfunction of endothelial cells-factors that promote atherosclerosis. An additional mechanism by which impaired mitochondrial integrity predisposes to clinical manifestations of vascular diseases relates to vascular cell growth. Mitochondrial function is required for normal vascular cell growth and function. Mitochondrial dysfunction can result in apoptosis, favoring plaque rupture. Subclinical episodes of plaque rupture accelerate the progression of hemodynamically significant atherosclerotic lesions. Flow-limiting plaque rupture can result in myocardial infarction, stroke, and ischemic/reperfusion damage. Much of what is known on reactive oxygen species generation and modulation comes from studies in cultured cells and animal models. In this review, we have focused on linking this large body of literature to the clinical syndromes that predispose humans to atherosclerosis and its complications.