靶向线粒体治疗心血管疾病：治疗潜力与障碍。
Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles.
机构信息
Ruth L. and David S. Gottesman Institute for Stem Cell, Regenerative Medicine Research, Department of Cell Biology and Stem Cell Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
出版信息
Nat Rev Cardiol. 2019 Jan;16(1):33-55. doi: 10.1038/s41569-018-0074-0.
Abstract
A large body of evidence indicates that mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. Over the past 2 decades, extraordinary efforts have been focused on the development of agents that specifically target mitochondria for the treatment of cardiovascular disease. Despite such an intensive wave of investigation, no drugs specifically conceived to modulate mitochondrial functions are currently available for the clinical management of cardiovascular disease. In this Review, we discuss the therapeutic potential of targeting mitochondria in patients with cardiovascular disease, examine the obstacles that have restrained the development of mitochondria-targeting agents thus far, and identify strategies that might empower the full clinical potential of this approach.
摘要
大量证据表明，线粒体功能障碍在多种心血管疾病的发病机制中起主要作用。在过去的 20 年中，人们集中精力开发专门针对线粒体的药物，以治疗心血管疾病。尽管进行了如此密集的研究，但目前尚无专门用于调节线粒体功能的药物可用于心血管疾病的临床治疗。在这篇综述中，我们讨论了针对心血管疾病患者靶向线粒体的治疗潜力，研究了迄今为止限制线粒体靶向药物开发的障碍，并确定了可能充分发挥这种方法临床潜力的策略。
相似文献
1
Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles.靶向线粒体治疗心血管疾病：治疗潜力与障碍。
Nat Rev Cardiol. 2019 Jan;16(1):33-55. doi: 10.1038/s41569-018-0074-0.
2
Targeting mitochondria for cardiac protection.靶向线粒体保护心脏。
Curr Drug Targets. 2013 May 1;14(5):586-600. doi: 10.2174/1389450111314050008.
3
Mitochondria-Targeted Antioxidants for the Treatment of Cardiovascular Disorders.用于治疗心血管疾病的线粒体靶向抗氧化剂
Adv Exp Med Biol. 2017;982:621-646. doi: 10.1007/978-3-319-55330-6_32.
4
Thymidine phosphorylase: A potential new target for treating cardiovascular disease.胸苷磷酸化酶：治疗心血管疾病的一个新靶点。
Trends Cardiovasc Med. 2018 Apr;28(3):157-171. doi: 10.1016/j.tcm.2017.10.003. Epub 2017 Oct 20.
5
Mitochondrial Dysfunction in Cardiovascular Aging.心血管衰老中的线粒体功能障碍
Adv Exp Med Biol. 2017;982:451-464. doi: 10.1007/978-3-319-55330-6_24.
6
Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies.线粒体功能障碍与心肌缺血再灌注：对新型疗法的启示
Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:535-565. doi: 10.1146/annurev-pharmtox-010715-103335.
7
Mitochondria as a drug target in ischemic heart disease and cardiomyopathy.线粒体作为缺血性心脏病和心肌病的药物靶点。
Circ Res. 2012 Oct 12;111(9):1222-36. doi: 10.1161/CIRCRESAHA.112.265660.
8
Targeting Cardiac Metabolic Pathways: A Role in Ischemic Management.靶向心脏代谢途径：在缺血管理中的作用
Vasc Health Risk Manag. 2020 Sep 14;16:353-365. doi: 10.2147/VHRM.S264130. eCollection 2020.
9
Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic approaches for cardiovascular diseases.线粒体活性氧是问题的核心：心血管疾病的新治疗方法。
Circ Res. 2015 May 22;116(11):1783-99. doi: 10.1161/CIRCRESAHA.116.305432.
10
The Future of Cardiovascular Therapeutics.心血管治疗的未来
Circulation. 2016 Jun 21;133(25):2610-7. doi: 10.1161/CIRCULATIONAHA.116.023555.
引用本文的文献
1
Association of C677T and A1298C Polymorphisms with First-Episode Myocardial Ischemia: A Case-Control Study.C677T和A1298C基因多态性与首发心肌缺血的关联：一项病例对照研究。
Genes (Basel). 2025 Jul 23;16(8):858. doi: 10.3390/genes16080858.
2
Age-Related Mitochondrial Alterations Contribute to Myocardial Responses During Sepsis.年龄相关的线粒体改变促成脓毒症期间的心肌反应。
Cells. 2025 Aug 7;14(15):1221. doi: 10.3390/cells14151221.
3
High-intensity interval training improves mitochondrial function and attenuates cardiomyocytes damage in ischemia-reperfusion.高强度间歇训练可改善线粒体功能并减轻缺血再灌注中的心肌细胞损伤。
Int J Cardiol Heart Vasc. 2025 Jul 25;60:101756. doi: 10.1016/j.ijcha.2025.101756. eCollection 2025 Oct.
4
Harnessing Mitochondrial Transplantation to Target Vascular Inflammation in Cardiovascular Health.利用线粒体移植靶向心血管健康中的血管炎症。
JACC Basic Transl Sci. 2025 Jul 25;10(8):101331. doi: 10.1016/j.jacbts.2025.101331.
5
A bibliometric and visualized analysis of research on mitochondria in myocardial ischemia from 2015 to 2024.2015年至2024年心肌缺血中线粒体研究的文献计量学与可视化分析
Front Cardiovasc Med. 2025 Jul 7;12:1547604. doi: 10.3389/fcvm.2025.1547604. eCollection 2025.
6
Inhibiting MARCH5/Mfn2 signaling as an alternative strategy to protect cardiomyocytes from hypoxia-induced mitochondrial dysfunction.抑制MARCH5/Mfn2信号传导作为保护心肌细胞免受缺氧诱导的线粒体功能障碍的替代策略。
Comput Struct Biotechnol J. 2025 Jul 2;27:3045-3065. doi: 10.1016/j.csbj.2025.07.001. eCollection 2025.
7
Involvement of Oxidative Stress in Mitochondrial Abnormalities During the Development of Heart Disease.氧化应激在心脏病发生发展过程中线粒体异常中的作用
Biomedicines. 2025 May 29;13(6):1338. doi: 10.3390/biomedicines13061338.
8
Mitochondrial Transplantation: A Novel Therapeutic Approach for Treating Diseases.线粒体移植：一种治疗疾病的新型治疗方法。
MedComm (2020). 2025 Jun 11;6(6):e70253. doi: 10.1002/mco2.70253. eCollection 2025 Jun.
9
The effects of SGLT2i on cardiac metabolism in patients with HFpEF: Fact or fiction?钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）对射血分数保留的心力衰竭（HFpEF）患者心脏代谢的影响：事实还是虚构？
Cardiovasc Diabetol. 2025 May 14;24(1):208. doi: 10.1186/s12933-025-02767-9.
10
Krüppel like factor 7 regulates mitochondrial dynamics balance in myocardial infarction.Krüppel样因子7调节心肌梗死中的线粒体动力学平衡。
Commun Biol. 2025 May 9;8(1):722. doi: 10.1038/s42003-025-08139-z.
本文引用的文献
1
SnapShot: CGAS-STING Signaling.快照：CGAS-STING 信号通路。
Cell. 2018 Mar 22;173(1):276-276.e1. doi: 10.1016/j.cell.2018.03.015.
2
Aspirin Recapitulates Features of Caloric Restriction.阿司匹林再现热量限制的特征。
Cell Rep. 2018 Feb 27;22(9):2395-2407. doi: 10.1016/j.celrep.2018.02.024.
3
Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury.细胞质 DNA 感应促进巨噬细胞转化并控制心肌缺血损伤。
Circulation. 2018 Jun 12;137(24):2613-2634. doi: 10.1161/CIRCULATIONAHA.117.031046. Epub 2018 Feb 1.
4
Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction.急性反式白藜芦醇补充治疗伴内皮功能障碍的高血压患者的有益作用。
Clin Exp Hypertens. 2018;40(3):218-223. doi: 10.1080/10641963.2017.1288741. Epub 2018 Feb 12.
5
MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.MitoQ 可改善压力超负荷引起的心力衰竭中的线粒体功能障碍。
Free Radic Biol Med. 2018 Mar;117:18-29. doi: 10.1016/j.freeradbiomed.2018.01.012. Epub 2018 Feb 2.
6
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.细胞死亡的分子机制：细胞死亡命名委员会 2018 年的建议。
Cell Death Differ. 2018 Mar;25(3):486-541. doi: 10.1038/s41418-017-0012-4. Epub 2018 Jan 23.
7
Building and decoding ubiquitin chains for mitophagy.构建和解析用于线粒体自噬的泛素链。
Nat Rev Mol Cell Biol. 2018 Jan 23;19(2):93-108. doi: 10.1038/nrm.2017.129.
8
Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy.用于评估线粒体结构、氧化应激和线粒体自噬的条件性 MitoTimer 报告小鼠。
Mitochondrion. 2019 Jan;44:20-26. doi: 10.1016/j.mito.2017.12.008. Epub 2017 Dec 20.
9
Physiological Mitochondrial Fragmentation Is a Normal Cardiac Adaptation to Increased Energy Demand.生理性线粒体碎片化是心脏对增加能量需求的正常适应。
Circ Res. 2018 Jan 19;122(2):282-295. doi: 10.1161/CIRCRESAHA.117.310725. Epub 2017 Dec 12.
10
Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide.用于心力衰竭治疗的新型线粒体靶向肽：依拉米肽的随机、安慰剂对照试验
Circ Heart Fail. 2017 Dec;10(12). doi: 10.1161/CIRCHEARTFAILURE.117.004389.
Zotero 插件