Kuznetsova Tatiana, Knez Judita
Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Box 7001, 3000, Leuven, Belgium.
Hypertension Division, Department of Internal Medicine, University Clinical Centre Ljubljana, Ljubljana, Slovenia.
Adv Exp Med Biol. 2017;982:347-358. doi: 10.1007/978-3-319-55330-6_19.
Heart failure is a complex progressive clinical syndrome which is initiated by risk factors (e.g., hypertension, obesity, and diabetes), then proceeds to asymptomatic maladaptive left ventricular remodeling and dysfunction, and finally evolves into clinically overt, symptomatic heart failure, disability, and death. The progression of left ventricular dysfunction is associated with changes in cardiac energy metabolism. Mitochondria play a central role in a variety of cardiomyocytes functions, including oxidative energy production, storage of calcium ions, and programmed cell death. The mitochondrial DNA (mtDNA) content correlates with the size and number of mitochondria, which change under different energy demands and oxidative stress. Experimental studies demonstrated that any genetic manipulation resulting in significantly decreased mtDNA could accelerate the ageing process and cause adverse myocardial remodeling and dysfunction. On the other hand, preservation of the mtDNA copy number in mouse hearts delays the development of heart failure after myocardial infarction. Recent general population study also demonstrated that echocardiographic indexes of left ventricular structure and function are significantly and independently associated with mtDNA content measured at peripheral blood cells in cross-sectional and longitudinal analyses. In this chapter, we will discuss the recent experimental, clinical and epidemiological data of the possible impact of mtDNA content on cardiac structure and function.
心力衰竭是一种复杂的进行性临床综合征，由风险因素（如高血压、肥胖和糖尿病）引发，随后发展为无症状的适应性不良左心室重构和功能障碍，最终演变为临床显性、有症状的心力衰竭、残疾和死亡。左心室功能障碍的进展与心脏能量代谢的变化有关。线粒体在多种心肌细胞功能中起核心作用，包括氧化能量产生、钙离子储存和程序性细胞死亡。线粒体DNA（mtDNA）含量与线粒体的大小和数量相关，在不同的能量需求和氧化应激下会发生变化。实验研究表明，任何导致mtDNA显著减少的基因操作都可能加速衰老过程，并导致不良的心肌重构和功能障碍。另一方面，小鼠心脏中mtDNA拷贝数的保留可延迟心肌梗死后心力衰竭的发展。最近的人群研究还表明，在横断面和纵向分析中，左心室结构和功能的超声心动图指标与外周血细胞中测量的mtDNA含量显著且独立相关。在本章中，我们将讨论mtDNA含量对心脏结构和功能可能影响的最新实验、临床和流行病学数据。
