三碘甲状腺原氨酸通过减少细胞凋亡和保存线粒体来保护梗死心肌

IF 7.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Domenico Cerullo, Polyxeni Mantzouratou, Angelo M. Lavecchia, Melissa Balsamo, Daniela Corna, Laura Brunelli, Christodoulos Xinaris
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引用次数: 0

摘要

心肌梗死(MI)是心力衰竭的主要原因,甲状腺激素(TH)信号在心功能和梗死后恢复中起着关键作用。尽管有证据表明TH在心脏病患者中的安全性,但不一致的治疗结果和对其机制的有限理解阻碍了临床转化。本研究旨在探讨心肌梗死后急性三碘甲状腺原氨酸(T3)的远期疗效,并阐明其心脏保护作用的机制。为此,在冻伤小鼠左心室(LV)梗死模型中,分别在损伤后立即和24 h后给予两剂(40 μg/kg) T3。T3可显著减少瘢痕扩张。损伤后28天的超声心动图分析显示,给予T3可改善左室重塑,防止左室肥厚。在分子水平上,T3可显著减少梗死周围区域的细胞凋亡,但不诱导心肌细胞增殖。此外,T3还能阻止长链酰基肉碱的积累和随后的线粒体损伤。这些研究结果表明,心肌梗死后急性T3治疗可通过限制梗死周围区域的细胞凋亡和保持线粒体功能和结构完整性来改善长期左室功能并减少左室重塑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Triiodothyronine protects infarcted myocardium by reducing apoptosis and preserving mitochondria

Myocardial infarction (MI) is a leading cause of heart failure, with thyroid hormone (TH) signaling playing a key role in heart function and postinfarct recovery. Despite evidence of TH administration's safety in cardiac patients, inconsistent therapeutic outcomes and limited understanding of its mechanisms hinder clinical translation. This study aims to investigate the long-term effect of acute triiodothyronine (T3) administration following MI and to elucidate the mechanisms of its cardioprotective actions. To this end, two doses (40 μg/kg) of T3 were administered immediately after injury and 24 h later in a cryoinjury mouse model of left ventricle (LV) infarction. Remarkably T3 administration significantly reduced scar expansion. Echocardiographic analysis conducted 28 days post-injury revealed that T3 administration improved LV remodeling and prevented LV hypertrophy. At molecular level, T3 administration strongly reduced apoptosis in the peri-infarcted area, without inducing cardiac cell proliferation. Furthermore, T3 prevented the accumulation of long-chain acylcarnitines and the subsequent mitochondrial damage. These findings demonstrate that acute T3 treatment following MI improves long-term LV function and reduces LV remodeling by limiting apoptosis in the peri-infarct region and by preserving mitochondrial function and structural integrity.

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来源期刊
Basic Research in Cardiology
Basic Research in Cardiology 医学-心血管系统
CiteScore
16.30
自引率
5.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards. Basic Research in Cardiology regularly receives articles from the fields of - Molecular and Cellular Biology - Biochemistry - Biophysics - Pharmacology - Physiology and Pathology - Clinical Cardiology
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