Calcineurin signaling promotes takotsubo syndrome

Author:

Bruns Bastian,Antoniou MarilenaORCID,Baier Irena,Joos MaximilianORCID,Sevinchan Meryem,Moog Marie-Christine,Dieterich Christoph,Friederich Hans-ChristophORCID,Khan HilalORCID,Wilson HeatherORCID,Herzog Wolfgang,Dawson Dana K.,Frey Norbert,Schultz Jobst-Hendrik,Backs JohannesORCID

Abstract

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome that mimics the symptoms of acute myocardial infarction and is often preceded by emotional and/or physical stress. There is currently no treatment for TTS. Here we show that injection of 2.5 mg kg−1of epinephrine (EPI) into mice recapitulates numerous features of human TTS, including increased myocardial damage and mortality in males. Gene set enrichment analysis of myocardial RNA sequencing after EPI injection revealed significant enrichment of calcineurin-dependent pro-inflammatory gene networks, which was more pronounced in male than in female mice, in agreement with observed sex discrepancies in the mouse phenotype. An increase in calcineurin activity was detected in the circulating cells of patients with TTS, suggesting a systemic nature of the syndrome. Preventive and therapeutic treatment of mice injected with EPI using calcineurin inhibitors cyclosporine and tacrolimus improved heart function and reduced myocardial injury. Our findings suggest that calcineurin inhibition could be a potential therapy for TTS.

Funder

Deutsche Forschungsgemeinschaft

Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg

Deutsches Zentrum für Herz-Kreislaufforschung

Bundesministerium für Bildung und Forschung

Deutsche Gesellschaft für Kardiologie-Herz und Kreislaufforschung.

Deutsche Herzstiftung

Publisher

Springer Science and Business Media LLC

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Insulin resistance in Takotsubo syndrome;ESC Heart Failure;2023-12-20

2. The Immunology of Takotsubo Syndrome;Frontiers in Immunology;2023-10-06

3. α2δ-1 as a New Target for Immunosuppressant-Induced Hypertension;Circulation Research;2023-09-15

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3