Astaxanthin Alleviates the Process of Cardiac Hypertrophy by Targeting the METTL3/Circ_0078450/MiR-338-3p/GATA4 Pathway

IF 1.2 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS International heart journal Pub Date : 2024-01-31 DOI:10.1536/ihj.23-423

Kelian Zhang, Huilin Zhuo, Jingyi Guo, Wei Wang, Ruozhu Dai

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Abstract

Astaxanthin (ASX) is a natural antioxidant with preventive and therapeutic effects on various human diseases. However, the role of ASX in cardiac hypertrophy and its underlying molecular mechanisms remain unclear.

Cardiomyocytes (AC16) were used with angiotensin-II (Ang-II) to mimic the cardiac hypertrophy cell model. The protein levels of hypertrophy genes, GATA4, and methyltransferase-like 3 (METTL3) were determined by western blot analysis. Cell size was assessed using immunofluorescence staining. The expression of circ_0078450, miR-338-3p, and GATA4 were analyzed by quantitative real-time PCR. Also, the interaction between miR-338-3p and circ_0078450 or GATA4 was confirmed by dual-luciferase reporter and RIP assays, and the regulation of METTL3 on circ_0078450 was verified by MeRIP and RIP assays.

ASX reduced the hypertrophy gene protein expression and cell size in Ang-II-induced AC16 cells. Circ_0078450 was promoted under Ang-II treatment, and ASX reduced circ_0078450 expression in Ang-II-induced AC16 cells. Circ_0078450 could sponge miR-338-3p to positively regulate GATA4 expression, and GATA4 overexpression overturned the suppressive effect of circ_0078450 knockdown on Ang-II-induced cardiomyocyte hypertrophy. Also, the inhibitory effect of ASX on Ang-II-induced cardiomyocyte hypertrophy could be reversed by circ_0078450 or GATA4 overexpression. In addition, METTL3 mediated the m6A methylation of circ_0078450 to enhance circ_0078450 expression. Moreover, METTL3 knockdown suppressed Ang-II-induced cardiomyocyte hypertrophy by inhibiting circ_0078450 expression.

Our data showed that ASX repressed cardiac hypertrophy by regulating the METTL3/circ_0078450/miR-338-3p/GATA4 axis.

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虾青素通过靶向 METTL3/Circ_0078450/MiR-338-3p/GATA4 通路缓解心脏肥大过程

虾青素（ASX）是一种天然抗氧化剂，对多种人类疾病具有预防和治疗作用。心肌细胞（AC16）与血管紧张素-II（Ang-II）一起用于模拟心脏肥大细胞模型。心肌细胞（AC16）与血管紧张素-II（Ang-II）一起模拟心脏肥大细胞模型，通过 Western 印迹分析确定肥大基因、GATA4 和甲基转移酶样 3（METTL3）的蛋白水平。细胞大小通过免疫荧光染色进行评估。通过实时定量 PCR 分析了 circ_0078450、miR-338-3p 和 GATA4 的表达。METTL3对circ_0078450的调控作用通过MeRIP和RIP实验得到了验证。ASX可降低Ang-II诱导的AC16细胞中肥大基因蛋白的表达和细胞体积。Circ_0078450能海绵状调节miR-338-3p，从而正向调节GATA4的表达，而GATA4的过表达能推翻circ_0078450敲除对Ang-II诱导的心肌细胞肥大的抑制作用。同时，ASX 对 Ang-II 诱导的心肌细胞肥大的抑制作用可被 circ_0078450 或 GATA4 的过度表达所逆转。此外，METTL3介导了circ_0078450的m6A甲基化，从而增强了circ_0078450的表达。我们的数据表明，ASX通过调节METTL3/circ_0078450/miR-338-3p/GATA4轴抑制了心肌细胞肥大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International heart journal 医学-心血管系统

CiteScore

2.50

自引率

6.70%

发文量

148

审稿时长

6-12 weeks

期刊介绍： Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.