Catecholamine induces endothelial dysfunction via Angiotensin II and intermediate conductance calcium activated potassium channel

Xuehui Fan; Guoqiang Yang; Zhen Yang; Stefanie Uhlig; Katherine Sattler; Karen Bieback; Nazha Hamdani; Ibrahim El-Battrawy; Daniel Duerschmied; Xiaobo Zhou; Ibrahim Akin

Biomedicine & Pharmacotherapy (Aug 2024)

Catecholamine induces endothelial dysfunction via Angiotensin II and intermediate conductance calcium activated potassium channel

Xuehui Fan,
Guoqiang Yang,
Zhen Yang,
Stefanie Uhlig,
Katherine Sattler,
Karen Bieback,
Nazha Hamdani,
Ibrahim El-Battrawy,
Daniel Duerschmied,
Xiaobo Zhou,
Ibrahim Akin

Affiliations

Xuehui Fan: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China; European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany; Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Corresponding authors at: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany.
Guoqiang Yang: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Acupuncture and Rehabilitation Department, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
Zhen Yang: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany
Stefanie Uhlig: Flow Core Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Katherine Sattler: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China
Karen Bieback: Flow Core Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Nazha Hamdani: Institute of Physiology, Department of Cellular and Translational Physiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany; Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany; Department of Cardiology and Angiology, Bergmannsheil University Hospital, Ruhr University Bochum, Bochum, Germany
Ibrahim El-Battrawy: Institute of Physiology, Department of Cellular and Translational Physiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany; Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany; Department of Cardiology and Angiology, Bergmannsheil University Hospital, Ruhr University Bochum, Bochum, Germany
Daniel Duerschmied: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China
Xiaobo Zhou: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China; European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany; Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Corresponding authors at: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany.
Ibrahim Akin: Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China

Journal volume & issue: Vol. 177
p. 116928

Abstract

Read online

Endothelial dysfunction contributes to the pathogenesis of Takotsubo syndrome (TTS). However, the exact mechanism underlying endothelial dysfunction in the setting of TTS has not been completely clarified. This study aims to investigate the roles of angiotensin II (Ang II) and intermediate-conductance Ca2+-activated K+ (SK4) channels in catecholamine-induced endothelial dysfunction. Human cardiac microvascular endothelial cells (HCMECs) were exposed to 100 µM epinephrine (Epi), mimicking the setting of TTS. Epi treatment increased the ET-1 concentration and reduced NO levels in HCMECs. Importantly, the effects of Epi were found to be mitigated in the presence of Ang II receptor blockers. Furthermore, Ang II mimicked Epi effects on ET-1 and NO production. Additionally, Ang II inhibited tube formation and increased cell apoptosis. The effects of Ang II could be reversed by an SK4 activator NS309 and mimicked by an SK4 channel blocker TRAM-34. Ang II also inhibited the SK4 channel current (ISK4) without affecting its expression level. Ang II could depolarize the cell membrane potential. Ang II promoted ROS release and reduced protein kinase A (PKA) expression. A ROS blocker prevented Ang II effect on ISK4. The PKA activator Sp-8-Br-cAMPS increased SK4 channel currents. Epinephrine enhanced the activity of ACE by activating the α1 receptor/Gq/PKC signal pathway, thereby promoting the secretion of Ang II. The study suggested that high-level catecholamine can increase Ang II release from endothelial cells by α1 receptors/Gq/PKC signal pathway. Ang II can inhibit SK4 channel current by increasing ROS generation and reducing PKA expression, thereby contributing to endothelial dysfunction.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

About the journal

Abstract

Keywords