Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
Hypertension Heart Failure Research Center, Chonnam National University Hospital, Gwangju, Korea.
J Cell Mol Med. 2022 Jul;26(14):4076-4086. doi: 10.1111/jcmm.17449. Epub 2022 Jun 19.
Gallic acid has been reported to mitigate cardiac hypertrophy, fibrosis and arterial hypertension. The effects of syringic acid, a derivative of gallic acid, on cardiac hypertrophy and fibrosis have not been previously investigated. This study aimed to examine the effects of syringic acid on isoproterenol-treated mice and cells. Syringic acid mitigated the isoproterenol-induced upregulation of heart weight to bodyweight ratio, pathological cardiac remodelling and fibrosis in mice. Picrosirius red staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses revealed that syringic acid markedly downregulated collagen accumulation and fibrosis-related factors, including Fn1. The results of RNA sequencing analysis of Ereg expression were verified using qRT-PCR. Syringic acid or transfection with si-Ereg mitigated the isoproterenol-induced upregulation of Ereg, Myc and Ngfr. Ereg knockdown mitigated the isoproterenol-induced upregulation of Nppb and Fn1 and enhancement of cell size. Mechanistically, syringic acid alleviated cardiac hypertrophy and fibrosis by downregulating Ereg. These results suggest that syringic acid is a potential therapeutic agent for cardiac hypertrophy and fibrosis.
没食子酸已被报道可减轻心肌肥厚、纤维化和动脉高血压。没食子酸的衍生物丁香酸对心肌肥厚和纤维化的影响尚未被研究过。本研究旨在探讨丁香酸对异丙肾上腺素处理的小鼠和细胞的影响。丁香酸减轻了异丙肾上腺素诱导的小鼠心脏重量与体重比、病理性心脏重构和纤维化的上调。天狼猩红染色、实时定量聚合酶链反应(qRT-PCR)和 Western blot 分析表明,丁香酸显著地下调了胶原积累和纤维化相关因子,包括 Fn1。Ereg 表达的 RNA 测序分析结果通过 qRT-PCR 得到验证。丁香酸或 si-Ereg 转染减轻了异丙肾上腺素诱导的 Ereg、Myc 和 Ngfr 的上调。Ereg 敲低减轻了异丙肾上腺素诱导的 Nppb 和 Fn1 的上调和细胞大小的增强。在机制上,丁香酸通过下调 Ereg 来减轻心肌肥厚和纤维化。这些结果表明,丁香酸是治疗心肌肥厚和纤维化的一种有潜力的治疗剂。