Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts

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 <i>n</i> = 23; ncRNA <i>n</i>...

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Autores principales:	Estefanía Tarazón, Lorena Pérez-Carrillo, Isaac Giménez-Escamilla, Pablo Ramos-Castellanos, Luis Martínez-Dolz, Manuel Portolés, Esther Roselló-Lletí
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ischaemic cardiomyopathy telomere <i>TERRA</i> and <i>GUARDIN</i> oxidative stress response Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d80e1050f5244168a801b07b6cbb6a09
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spelling	oai:doaj.org-article:d80e1050f5244168a801b07b6cbb6a092021-11-25T16:27:48ZRelationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts10.3390/antiox101117502076-3921https://doaj.org/article/d80e1050f5244168a801b07b6cbb6a092021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1750https://doaj.org/toc/2076-3921Although 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 <i>n</i> = 23; ncRNA <i>n</i> = 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 <i>RAD51D</i> 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 (<i>TERRA</i> and <i>GUARDIN)</i> involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the <i>TERRA</i> transcription factor <i>ATF7</i> was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of <i>GUARDIN</i> and its transcription factor <i>FOSL2</i> 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.Estefanía TarazónLorena Pérez-CarrilloIsaac Giménez-EscamillaPablo Ramos-CastellanosLuis Martínez-DolzManuel PortolésEsther Roselló-LletíMDPI AGarticleischaemic cardiomyopathytelomere<i>TERRA</i> and <i>GUARDIN</i>oxidative stress responseTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1750, p 1750 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischaemic cardiomyopathy telomere <i>TERRA</i> and <i>GUARDIN</i> oxidative stress response Therapeutics. Pharmacology RM1-950
spellingShingle	ischaemic cardiomyopathy telomere <i>TERRA</i> and <i>GUARDIN</i> oxidative stress response Therapeutics. Pharmacology RM1-950 Estefanía Tarazón Lorena Pérez-Carrillo Isaac Giménez-Escamilla Pablo Ramos-Castellanos Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
description	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 <i>n</i> = 23; ncRNA <i>n</i> = 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 <i>RAD51D</i> 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 (<i>TERRA</i> and <i>GUARDIN)</i> involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the <i>TERRA</i> transcription factor <i>ATF7</i> was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of <i>GUARDIN</i> and its transcription factor <i>FOSL2</i> 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.
format	article
author	Estefanía Tarazón Lorena Pérez-Carrillo Isaac Giménez-Escamilla Pablo Ramos-Castellanos Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí
author_facet	Estefanía Tarazón Lorena Pérez-Carrillo Isaac Giménez-Escamilla Pablo Ramos-Castellanos Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí
author_sort	Estefanía Tarazón
title	Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
title_short	Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
title_full	Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
title_fullStr	Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
title_full_unstemmed	Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts
title_sort	relationships of telomere homeostasis with oxidative stress and cardiac dysfunction in human ischaemic hearts
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d80e1050f5244168a801b07b6cbb6a09
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Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts

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