Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Department of Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, PR China.
Transl Res. 2024 Oct;272:54-67. doi: 10.1016/j.trsl.2024.05.009. Epub 2024 Jun 3.
Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration.
Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype.
LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.
动脉重构是心血管疾病发病机制中的一种常见病理生理改变，其中血管平滑肌细胞（VSMC）的表型转换起着重要作用。最近，越来越多的长链非编码 RNA（lncRNA）被证明能够编码发挥生物学作用且具有巨大临床转化潜力的微小肽。然而，lncRNA 编码的微小肽在动脉重构中的作用尚未得到很好的研究，需要进一步探索。
通过生物信息学分析和实验验证，我们发现一种新的 lncRNA，线粒体功能相关 lncRNA（MFRL），编码一个 64 个氨基酸的微小肽 MFRLP。MFRL 和 MFRLP 在 VSMC 的表型转换中发挥重要作用。进一步的实验表明，MFRLP 与线粒体细胞色素 b 相互作用，减少活性氧的积累，抑制线粒体自噬，并抑制 VSMC 从收缩型向合成型的表型转换。
lncRNA MFRL 编码的微小肽 MFRLP 与线粒体细胞色素 b 相互作用，抑制 VSMC 从收缩型向合成型的表型转换，改善动脉重构。
