Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling

Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiolog...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yang Y, Wang H, Song N, Jiang Y, Zhang J, Meng X, Feng X, Liu H, Peng K, Ji F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	myocardial ischemia/reperfusion injury dexmedetomidine endoplasmic reticulum stress inflammation apoptosis grp78/perk/chop Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/3649104b7f784a75a5f83725010d860b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3649104b7f784a75a5f83725010d860b
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	myocardial ischemia/reperfusion injury dexmedetomidine endoplasmic reticulum stress inflammation apoptosis grp78/perk/chop Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	myocardial ischemia/reperfusion injury dexmedetomidine endoplasmic reticulum stress inflammation apoptosis grp78/perk/chop Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Yang Y Wang H Song N Jiang Y Zhang J Meng X Feng X Liu H Peng K Ji F Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
description	Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Transitional Residency Program, Intermountain Medical Center, Murray, UT, USA; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comBackground: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α 2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment.Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α 2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312.Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.Keywords: myocardial ischemia/reperfusion injury, dexmedetomidine, endoplasmic reticulum stress, inflammation, apoptosis, GRP78/PERK/CHOP
format	article
author	Yang Y Wang H Song N Jiang Y Zhang J Meng X Feng X Liu H Peng K Ji F
author_facet	Yang Y Wang H Song N Jiang Y Zhang J Meng X Feng X Liu H Peng K Ji F
author_sort	Yang Y
title	Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
title_short	Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
title_full	Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
title_fullStr	Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
title_full_unstemmed	Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling
title_sort	dexmedetomidine attenuates ischemia/reperfusion-induced myocardial inflammation and apoptosis through inhibiting endoplasmic reticulum stress signaling
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/3649104b7f784a75a5f83725010d860b
work_keys_str_mv	AT yangy dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT wangh dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT songn dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT jiangy dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT zhangj dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT mengx dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT fengx dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT liuh dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT pengk dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling AT jif dexmedetomidineattenuatesischemiareperfusioninducedmyocardialinflammationandapoptosisthroughinhibitingendoplasmicreticulumstresssignaling
_version_	1718391419996995584
spelling	oai:doaj.org-article:3649104b7f784a75a5f83725010d860b2021-12-02T14:24:23ZDexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling1178-7031https://doaj.org/article/3649104b7f784a75a5f83725010d860b2021-03-01T00:00:00Zhttps://www.dovepress.com/dexmedetomidine-attenuates-ischemiareperfusion-induced-myocardial-infl-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Transitional Residency Program, Intermountain Medical Center, Murray, UT, USA; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comBackground: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α 2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment.Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α 2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312.Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.Keywords: myocardial ischemia/reperfusion injury, dexmedetomidine, endoplasmic reticulum stress, inflammation, apoptosis, GRP78/PERK/CHOPYang YWang HSong NJiang YZhang JMeng XFeng XLiu HPeng KJi FDove Medical Pressarticlemyocardial ischemia/reperfusion injurydexmedetomidineendoplasmic reticulum stressinflammationapoptosisgrp78/perk/chopPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1217-1233 (2021)

Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling

Ejemplares similares