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Maternal exercise represses FGF21 via SIRT1 to improve the phenotypic transformation of vascular smooth muscle in hypertensive offspring

Hypertension Research volume 48, pages 353–365 (2025)Cite this article

Abstract

Maternal exercise during pregnancy is widely recognized as an effective means of promoting cardiovascular health in offspring. Few studies have explored how maternal exercise impacts vascular function and phenotypic switching in hypertensive offspring, despite the known involvement of vascular structural and functional remodeling in hypertension pathogenesis. Research indicates a significant relationship between elevated blood pressure and fibroblast growth factor 21 (FGF21) levels. It remains unclear whether maternal exercise during pregnancy can improve vascular function in hypertensive offspring by regulating FGF21 and its underlying mechanisms. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were randomly assigned to either a sedentary or exercise group. The exercise group underwent weightless swimming exercise from gestation day 1 (GD1) to GD20. The aim was to investigate the epigenetic modifications mediated by histone deacetylase sirtuin 1 (SIRT1) during the fetal period and the phenotypic changes in the mesenteric arteries (MAs) of hypertensive offspring. We found that maternal exercise significantly improved vascular remodeling in hypertensive offspring. Specifically, maternal exercise upregulated SIRT1 expression, which led to decreased H3K9ac (histone H3 lysine 9 acetylation) in the promoter region of the FGF21 gene. This epigenetic modification resulted in the transcriptional downregulation of FGF21 in the MAs of hypertensive fetuses. These results suggest that maternal exercise may lower blood pressure in hypertensive offspring by regulating deacetylation of the FGF21 gene promoter region through SIRT1, thereby reversing phenotypic switching and vascular structural remodeling.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (32371183, 32200941, and 32071174), the National Key Research and Development Program of China (2022YFC3600201), and the Fundamental Research Funds for the Central Universities (2024JCYJ001 and 2024YJSY002).

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Authors and Affiliations

  1. Department of Exercise Physiology, Beijing Sport University, 100084, Beijing, China

    Meiling Shan, Fang Qiu, Peng Li, Yanyan Zhang & Lijun Shi

  2. School of Physical Education, Hubei University, 430062, Wuhan, China

    Meiling Shan

  3. Laboratory of Sports Stress and Adaptation of General Administration of Sport, Beijing University, Beijing, 100084, China

    Yanyan Zhang & Lijun Shi

  4. Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, 100084, Beijing, China

    Yanyan Zhang & Lijun Shi

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  1. Meiling Shan
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Correspondence to Lijun Shi.

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Shan, M., Qiu, F., Li, P. et al. Maternal exercise represses FGF21 via SIRT1 to improve the phenotypic transformation of vascular smooth muscle in hypertensive offspring. Hypertens Res 48, 353–365 (2025). https://doi.org/10.1038/s41440-024-01991-2

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