Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK-Sirt1 and inactivating TGFβ1-Smad2/3

IF 5.6 2区医学 Q1 PHYSIOLOGY

Acta Physiologica Pub Date : 2024-05-16 DOI:10.1111/apha.14163

Hangzhuo Li, Shuguang Qin, Jie Tang, Tao Wang, Wujing Ren, Lingyun Di, Wenyan Bo, Yixuan Ma, Fangnan Wu, Zujie Xu, Wei Song, Mengxin Cai, Yue Xi, Zhenjun Tian

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引用次数: 0

Abstract

Aim

To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI).

Methods

The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5^−/−). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H₂O₂, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR.

Results

Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFβ1-TGFβR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFβ1-Smad2/3 pathway, and promoted apoptosis in H₂O₂-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFβR2 expression, were attenuated by LV-Sirt1 shRNA.

Conclusion

Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFβ1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.

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阻力运动通过激活 AMPK-Sirt1 和灭活 TGFβ1-Smad2/3，上调 Irisin 的表达并抑制心肌梗死后的心肌纤维化。

目的：揭示鸢尾素在阻力运动对心肌梗死（MI）小鼠心肌纤维化（MF）和心功能的有益影响中的作用：方法：通过结扎Fndc5基因敲除小鼠（Fndc5-/-）的左前降支冠状动脉建立心肌梗死模型。术后一周开始阻力运动，并持续四周。此外，还使用 H2O2、AICAR、重组人 Irisin 蛋白（rhIRISIN）和 Sirt1 shRNA 慢病毒（LV-Sirt1 shRNA）干预原代离体心脏成纤维细胞（CFs）。通过 Masson 染色观察 MF，并使用 TUNEL 染色评估细胞凋亡。用生化试剂盒检测 MDA 和 T-SOD 含量。蛋白质和基因的表达通过 Western 印迹和 RT-qPCR 进行检测：结果：阻力运动提高了Fndc5 mRNA水平，抑制了TGFβ1-TGFβR2-Smad2/3通路的激活，激活了AMPK-Sirt1通路，降低了梗死心脏的氧化应激、细胞凋亡和MF水平，促进了心脏功能。然而，Fndc5基因敲除削弱了阻力运动对心肌梗死心脏的保护作用。体外实验结果表明，AICAR 和 rhIRISIN 的干预激活了 AMPK-Sirt1 通路，灭活了 TGFβ1-Smad2/3 通路，并促进了 H2O2 处理的 CFs 的细胞凋亡。值得注意的是，除了TGFβR2的表达外，rhIRISIN干预的这些效应都被LV-Sirt1 shRNA所减弱：结论：阻力运动可上调 Fndc5 的表达，激活 AMPK-Sirt1 通路，抑制 TGFβ1-Smad2/3 通路的激活，减轻 MF，促进心肌梗死后的心功能。

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

Acta Physiologica 医学-生理学

CiteScore

11.80

自引率

15.90%

发文量

182

审稿时长

4-8 weeks

期刊介绍： Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.