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Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway

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Abstract

Objective

Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure. Thus, there is an urgent need for more effective strategies to aid in cardiac protection. Our previous work found that sphingosine-1-phosphate (S1P) could ameliorate cardiac hypertrophy. In this study, we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling.

Methods

Eight-week-old male C57BL/6 mice were randomly divided into a sham, transverse aortic constriction (TAC) or a TAC+S1P treatment group.

Results

We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease in α-smooth muscle actin (α-SMA) and collagen type I (COL I) expression compared with the TAC group. We also found that one of the key S1P enzymes, sphingosine kinase 2 (SphK2), which was mainly distributed in cytoblasts, was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro. In addition, our in vitro results showed that S1P treatment activated extracellular regulated protein kinases (ERK) phosphorylation mainly through the S1P receptor 2 (S1PR2) and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine.

Conclusion

These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart. This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

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Authors and Affiliations

  1. Wuhan No. 4 Hospital, Wuhan Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hui Yan

  2. Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hu Zhao, Shao-wei Yi, Hang Zhuang, Dao-wen Wang & Jian-gang Jiang

  3. Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Gui-fen Shen

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  1. Hui Yan
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  2. Hu Zhao
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  3. Shao-wei Yi
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  4. Hang Zhuang
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Correspondence to Gui-fen Shen.

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Additional information

This work was supported by the National Natural Science Foundation of China (No. 81873505).

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Yan, H., Zhao, H., Yi, Sw. et al. Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway. CURR MED SCI 42, 702–710 (2022). https://doi.org/10.1007/s11596-022-2600-x

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  • DOI: https://doi.org/10.1007/s11596-022-2600-x

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