Cerullo Domenico, Mantzouratou Polyxeni, Lavecchia Angelo M, Balsamo Melissa, Corna Daniela, Brunelli Laura, Xinaris Christodoulos
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Molecular Medicine, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87, 24126, Bergamo, Italy.
Environmental Health Sciences Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156, Milan, Italy.
Basic Res Cardiol. 2025 Apr 15. doi: 10.1007/s00395-025-01106-z.
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.
心肌梗死（MI）是心力衰竭的主要原因，甲状腺激素（TH）信号传导在心脏功能和梗死后恢复中起关键作用。尽管有证据表明TH给药对心脏病患者安全，但治疗效果不一致以及对其机制的了解有限阻碍了临床转化。本研究旨在探讨心肌梗死后急性给予三碘甲状腺原氨酸（T3）的长期影响，并阐明其心脏保护作用的机制。为此，在左心室（LV）梗死的冷冻损伤小鼠模型中，损伤后立即及24小时后给予两剂（40μg/kg）T3。值得注意的是，给予T3可显著减少瘢痕扩展。损伤后28天进行的超声心动图分析显示，给予T3可改善左心室重构并预防左心室肥厚。在分子水平上，给予T3可强烈减少梗死周边区域的细胞凋亡，而不会诱导心脏细胞增殖。此外，T3可防止长链酰基肉碱的积累及随后的线粒体损伤。这些发现表明，心肌梗死后急性T3治疗可通过限制梗死周边区域的细胞凋亡以及保留线粒体功能和结构完整性来改善长期左心室功能并减少左心室重构。
