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Aerobic exercise improves BKCa channel-mediated vasodilation in diabetic vascular smooth muscle via AMPK/Nrf2/HO-1 pathway

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Abstract

Aims

This study aims to investigate the effect of aerobic exercise training on BKCa channel in diabetic vascular smooth muscle and explore the underlying mechanism.

Methods

Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured.

Results

Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BKCa-mediated vasodilation, a higher level of ROS, and a lower expression of BKCa α, BKCa β1, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. Exercise training increased the expression of BKCa α, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BKCa α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions.

Conclusions

BKCa channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BKCa channel and improve BKCa-mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway.

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Funding

This analysis was based upon work funded by the Natural Science Foundation of the Jiangsu Education Institutions of China (Grant No. 22KJB180017) and Xuzhou Natural Science Foundation (Grant No. KC21029).

Author information

Authors and Affiliations

  1. Department of Physical Education, Jiangsu Normal University, Xuzhou, China

    Yujia Liu & Yue Cheng

  2. Caoxian People’s Hospital, Heze, China

    Na Xiang

  3. China Institute of Sport and Health Science, Beijing Sport University, Beijing, China

    Zhiyuan Wang, Siyu Li & Lijing Gong

  4. Biomedical R&d Center, School of Life Science, Jiangsu Normal University, Tongshan District, No. 101, Shanghai Road, Xuzhou, Jiangsu, China

    Xingqi Wang

Authors
  1. Yujia Liu
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  2. Yue Cheng
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  4. Zhiyuan Wang
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  5. Siyu Li
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  6. Lijing Gong
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Contributions

YL and XW designed the research. Material preparation, data collection, and analysis were performed by YL, YC, NX, ZW, SL, and LG. The first draft of the manuscript was written by YL, YC, and XW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xingqi Wang.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The animal studies were approved by the Animal Care and Use Committee of Beijing Sport University (No. 2020147A).

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Liu, Y., Cheng, Y., Xiang, N. et al. Aerobic exercise improves BKCa channel-mediated vasodilation in diabetic vascular smooth muscle via AMPK/Nrf2/HO-1 pathway. Acta Diabetol 61, 425–434 (2024). https://doi.org/10.1007/s00592-023-02210-z

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  • DOI: https://doi.org/10.1007/s00592-023-02210-z

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