Tarazón Estefanía, Pérez-Carrillo Lorena, Giménez-Escamilla Isaac, Ramos-Castellanos Pablo, Martínez-Dolz Luis, Portolés Manuel, Roselló-Lletí Esther
Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
CIBERCV, Institute of Health Carlos III, C/Monforte de Lemos 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain.
Antioxidants (Basel). 2021 Nov 1;10(11):1750. doi: 10.3390/antiox10111750.
Although the roles of telomeres and oxidative stress in ischaemic cardiomyopathy (ICM) are known, mechanisms of telomere homeostasis and their relationship with oxidative stress are incompletely understood. We performed two RNA-seq analyses (mRNA = 23; ncRNA = 30) and protein validation on left ventricles of explanted hearts from ICM and control subjects. We observed dysregulation of the shelterin and cohesin complexes, which was related to an increase in the response to cellular oxidative stress. Moreover, we found alterations at mRNA level in the mechanisms of telomeric DNA repair. Specifically, increased mRNA levels were correlated with left ventricular diameters. RAD51D protein levels were unaltered, however, and were inversely corelated with the miR-103a-3p upregulation. We also observed the overexpression of lncRNAs ( and involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the transcription factor was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of and its transcription factor were correlated with those of catalase. Therefore, we showed specific alterations in the mechanisms of telomeric DNA repair and protection, and these alterations are related to an increase in the response mechanisms to oxidative stress and cardiac dysfunction in ICM.
尽管端粒和氧化应激在缺血性心肌病（ICM）中的作用已为人所知，但端粒稳态机制及其与氧化应激的关系仍未完全阐明。我们对ICM患者和对照受试者的离体心脏左心室进行了两次RNA测序分析（mRNA = 23；非编码RNA = 30）以及蛋白质验证。我们观察到了端粒保护蛋白和黏连蛋白复合物的失调，这与细胞氧化应激反应的增加有关。此外，我们发现端粒DNA修复机制在mRNA水平上发生了改变。具体而言，mRNA水平的升高与左心室直径相关。然而，RAD51D蛋白水平未发生改变，且与miR-103a-3p的上调呈负相关。我们还观察到了长链非编码RNA的过表达（以及 参与应激反应中端粒保护及其调节分子的改变。转录因子 的表达与超氧化物歧化酶1的表达及左心室直径相关。 和其转录因子 的水平与过氧化氢酶的水平相关。因此，我们发现了端粒DNA修复和保护机制中的特定改变，这些改变与ICM中氧化应激反应机制的增加及心脏功能障碍有关。
