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Klotho improves cardiac fibrosis, inflammatory cytokines, ferroptosis, and oxidative stress in mice with myocardial infarction

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Abstract

The anti-aging protein Klotho has been associated with cardiovascular health protection. Nevertheless, the protective mechanism remains unknown. The present study is aimed at exploring the effect of Klotho on cardiac remodeling and its potential mechanism in mice with myocardial infarction (MI). We used left anterior coronary artery descending ligation to develop an MI model for in vivo analyses. In contrast, H9C2 cells and cardiac fibroblasts were used to establish the oxygen–glucose deprivation (OGD) model in in vitro analyses. In vivo and in vitro models were treated with Klotho. Compound C, an AMPK signaling inhibitor, was used to determine whether Klotho’s effects are mediated through the AMPK/mTOR signaling pathway. Echocardiography, Masson trichrome staining, immunofluorescence, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot were used to detect the related indicators. The findings of the in vivo model indicate that Klotho treatment improved the mice’s cardiac function, reduced cardiac fibrosis, and attenuated myocardial inflammatory factors, ferroptosis, and oxidative stress. The results of the in vitro model were in line with the findings of in vivo modeling. An AMPK inhibitor, Compound C, reversed all these effects. In conclusion, Klotho potentially improves cardiac remodeling in MI mice by regulating AMPK/mTOR signaling, demonstrating Klotho as an effective MI therapeutic agent.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81871359 and No. 82071944).

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Author notes

  1. Kai WANG, Zhongming LI, and Yinzhang DING contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Kai WANG, Yinzhang DING, Zheng LIU & Wei ZHENG

  2. Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    Zhongming LI, Yansong LI, Xianling LIU, Yan SUN, Jian HONG, Lijun QIAN & Di XU

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  1. Kai WANG
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  2. Zhongming LI
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Contributions

Kai WANG designed the study and completed the experiment together with Zhongming LI and Yinzhang DING. The first draft was written by Kai WANG, and the other authors participated in the revision and polishing of the draft. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Di XU.

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Ethics approval

The protocols for animal experiments followed NIH guidelines. Nanjing Medical University’s ethics committee has approved the study (IACUC-2102002). ARRIVE guidelines were followed in the design of animal experiments.

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Keypoints.

Klotho ameliorates cardiac function, reduces cardiac fibrosis, and attenuates myocardial inflammatory factors in mice with myocardial infarction.

Klotho improves ferroptosis and oxidative stress in mice with myocardial infarction.

Klotho potentially improves cardiac remodeling in MI mice by regulating AMPK/mTOR signaling.

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WANG, K., LI, Z., DING, Y. et al. Klotho improves cardiac fibrosis, inflammatory cytokines, ferroptosis, and oxidative stress in mice with myocardial infarction. J Physiol Biochem 79, 341–353 (2023). https://doi.org/10.1007/s13105-023-00945-5

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