The effects of hypothalamic microglial activation on ventricular arrhythmias in stress cardiomyopathy
Peng-Qi LIN1
Quan-Wei PEI1
Bin LI1
Jie-Mei YANG2
Li-Na ZOU1
De-Zhan SU1
Jun-Pei ZHANG1
Hong-Peng YIN1
Mbabazi Nadine1
Jun-Jie YANG1
Nevzorova Vera A3
Khan Musawir Abbas1
Zhao-Lei JIANG4
Jing-Jie LI1
De-Chun YIN5
1.Department of Cardiology,the First Affiliated Hospital of Harbin Medical University,Harbin,China2.Department of Echocardiography,the First Affiliated Hospital of Harbin Medical University,Harbin,China3.Institute Therapy and Instrumental Diagnostic,Pacific State Medical University,Vladivostok,Russia4.Department of Cardiothoracic Sur-gery,Xinhua Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai,China5.Department of Geriatrics,the First Affiliated Hospital of Harbin Medical University,Harbin,China
摘要：Background Stress cardiomyopathy(SCM)currently has a high incidence in older adults,and the theories regarding its causes include"catecholamine myocardial toxicity"and"sympathetic hyperactivation".However,the role of the central nervous system in the pathogenesis of SCM remains unknown.We investigated the role of microglia activation in the paraventricular hypoth-alamic nucleus(PVN)in the development of SCM.
Methods An SCM model was created using male Sprague-Dawley(SD)rats,immobilized for 6 h every day for a week.Electroca-rdiogram,cardiac electrophysiology,and echocardiography examinations were performed to verify the changes in cardiac struc-ture and function in rats with SCM.RNA sequencing was used to explore the changes in the hypothalamus during SCM.In addition,brain and heart tissues were collected to detect microglial activation and sympathetic activity.
Results The main findings were as follows:(1)immobilization stress successfully induced SCM in SD rats;(2)microglia were sig-nificantly activated in the hypothalamus,as evidenced by cytosol thickening,increases in the number of microglial branches,and microglia enriched in the PVN;(3)in SCM,the microglia in the PVN exhibited increased central and peripheral cardiac sympath-etic activity and increased the expression of neuroinflammatory factors;and(4)it is possible that inhibiting microglial activation co-uld suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats.
Conclusions SCM was induced in SD rats by immobilization stress,acting through the activation of the hypothalamic micr-oglia.The activated microglia were specifically enriched in the PVN,increasing the activity of the central and peripheral sympat-hetic nervous systems by regulating the expression of neuro-inflammatory factors,mediating dysfunction of the left ventricle,and increasing the susceptibility to ventricular arrhythmias.
机标关键词：stressactivationarrhythmiascardiomyopathyeffectshypothalamicmicroglialventricular
论文发表日期：2024-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 1119-1132 )