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A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation

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机构： [1]Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [2]Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [3]Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [4]Department of Cardiology, Southern University of Science and Technology Hospital, Shenzhen, Guangdong, China

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关键词： Atrial fibrillation tRNA-derived small RNAs tsRNA-5008a Ferroptosis

摘要：

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.Copyright © 2024 Elsevier Inc. All rights reserved.

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出版当年[2023]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

第一作者：

第一作者机构： [1]Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

通讯作者：

通讯机构： [1]Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [2]Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China [*1]Department of Geriatrics, Nanfang Hospital, Southern Medical University, North No. 1838, Guangzhou Avenue, Guangzhou, Guangdong, 510515, China [*2]Department of Cardiology, Nanfang Hospital, Southern Medical University, North No. 1838, Guangzhou Avenue, Guangzhou, Guangdong, 510515, China.

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