State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
J Mol Cell Cardiol. 2024 Jun;191:7-11. doi: 10.1016/j.yjmcc.2024.04.007. Epub 2024 Apr 10.
Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.
新生鼠心脏在受伤后可以再生，而成年心脏则形成纤维疤痕。甲状腺激素信号在心脏再生中的机制值得进一步研究。我们发现，三碘甲状腺原氨酸在顶端切除后会损害新生鼠心肌细胞的增殖和心脏再生。对心脏 CD45 阳性白细胞进行单细胞 RNA 测序显示，三碘甲状腺原氨酸处理后单核细胞/巨噬细胞表现出炎症表型。此外，我们观察到三碘甲状腺原氨酸处理的巨噬细胞培养基抑制了心肌细胞的增殖，而三碘甲状腺原氨酸本身在体外对心肌细胞没有直接影响。我们的研究揭示了三碘甲状腺原氨酸在介导抑制心脏再生的炎症反应中的新作用。
