SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines

Hong‐Xia Guo; Run‐Nan Tantai; Bin Yang; Li‐Guo Yang; Yuan Ma; Hui‐Ping Zhao; Jing Wang; Xiao‐Juan Zhang; Rui‐Hua Wang; Fei Wang; Jia‐Pu Wang; Rui‐Fang Chi; Fu‐Zhong Qin; Ya‐Xin Liu

doi:10.1111/bph.70005

journal article Mar 10, 2025

SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines

Hong‐Xia Guo Run‐Nan Tantai Bin Yang

Li‐Guo Yang Yuan Ma

Hui‐Ping Zhao Jing Wang

Xiao‐Juan Zhang Rui‐Hua Wang Fei Wang

Jia‐Pu Wang Rui‐Fang Chi Fu‐Zhong Qin

Ya‐Xin Liu

British Journal of Pharmacology Vol. 182 No. 12 pp. 2772-2789 · Wiley

View at Publisher Save 10.1111/bph.70005

Abstract

Background and PurposeSphingosine‐1‐phosphate (S1P)/S1P receptor signalling exerts cardioprotective effects. However, the effect of the selective S1P1 receptor agonist SEW2871 on myocyte necroptosis in heart failure and the underlying mechanisms are unknown. In the present study, we tested the hypothesis that SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines.Experimental ApproachEight‐week‐old male C57BL/6J mice underwent myocardial infarction (MI) or sham operation. The animals were randomized to receive SEW2871 (5 mg·kg−1·day−1, i.p) or placebo for 4 weeks.Key ResultsMI mice exhibited the increases in left ventricular (LV) end‐diastolic dimension, LV end‐systolic dimension, LV mass and lung weight and a decrease in LV ejection fraction, indicating LV dilation, LV systolic dysfunction and lung congestion, and these alterations were attenuated by the SEW2871 treatment. Myocardial expression of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a marker of oxidative stress, inflammatory cytokines tumour necrosis factor‐α (TNF‐α), interleukin‐1β and interleukin‐6, and phosphorylated RIPK1 (p‐RIPK1), p‐RIPK3 and p‐MLKL, reflective of their respective kinase activities, markers of necroptosis, was markedly increased in the MI placebo group, and the increase was abolished by the SEW2871 treatment. Similarly, intracellular levels of reactive oxygen species, inflammatory cytokines, p‐RIPK1, p‐RIPK3 and p‐MLKL protein expression were increased in H9C2 cardiomyocytes under mimic ischaemia and the increases were prevented by the SEW2871 treatment.Conclusion and ImplicationsThe selective S1P1 receptor agonist SEW2871 attenuates myocyte necroptosis through inhibition of oxidative stress and inflammatory cytokines, leading to improvement of LV remodelling and function in heart failure.

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References

52

[1]

10.1016/j.bbadis.2019.165552

[2]

10.3389/fphar.2017.00645

[3]

10.1111/bph.16177

[4]

10.1111/bph.14112

[5]

10.3389/fphar.2017.00556

[6]

10.11909/j.issn.1671-5411.2018.05.003

[7]

10.1111/1440-1681.13583

[8]

Planning experiments: Updated guidance on experimental design and analysis and their reporting III

Michael J. Curtis, Stephen P. H. Alexander, Giuseppe Cirino et al.

British Journal of Pharmacology 10.1111/bph.15868

[9]

Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease

Dominic P. Del Re, Dulguun Amgalan, Andreas Linkermann et al.

Physiological Reviews 10.1152/physrev.00022.2018

[10]

10.1016/j.lfs.2018.01.023

[11]

10.1161/01.res.49.3.618

[12]

Necroptosis in heart disease: Molecular mechanisms and therapeutic implications

Xiaoyun Guo, Yi Chen, Qinghang Liu

Journal of Molecular and Cellular Cardiology 10.1016/j.yjmcc.2022.05.006

[13]

10.1007/s00395-013-0359-8

[14]

10.1093/cvr/cvp137

[15]

10.1016/j.jphs.2022.12.009

[16]

10.1111/1440-1681.13465

[17]

Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology

E. Jozefczuk, T.J. Guzik, M. Siedlinski

Pharmacological Research 10.1016/j.phrs.2020.104793

[18]

10.1016/j.bbalip.2012.06.006

[19]

Knapp M. "Cardioprotective role of sphingosine‐1‐phosphate" Journal of Physiology and Pharmacology (2011)

[20]

10.1097/shk.0000000000001270

[21]

10.1093/cvr/cvaa046

[22]

10.1016/j.bbadis.2015.01.010

[23]

10.1111/bph.15178

[24]

10.1093/cvr/cvu146

[25]

10.1038/s41598-024-57090-2

[26]

10.1161/01.res.0000261924.76669.36

[27]

Inflammation in Heart Failure

Sean P. Murphy, Rahul Kakkar, Cian P. McCarthy et al.

Journal of the American College of Cardiology 10.1016/j.jacc.2020.01.014

[28]

10.1016/j.yjmcc.2017.06.008

[29]

10.1038/nrcardio.2014.189

[30]

10.1113/jp280389

[31]

10.1002/1873-3468.14973

[32]

10.1186/s12929-021-00722-w

[33]

10.1007/s10741-016-9536-9

[34]

10.1002/ehf2.14176

[35]

10.1016/j.freeradbiomed.2007.04.021

[36]

10.1007/s00059-019-4785-8

[37]

10.1161/circulationaha.115.012427

[38]

10.3390/ijms222313053

[39]

10.1007/s11897-017-0337-9

[40]

10.3390/ijms22157831

[41]

10.3389/fphys.2013.00042

[42]

10.1097/fjc.0000000000000031

[43]

10.1016/j.lfs.2016.01.018

[44]

10.3390/ijms241311192

[45]

10.1161/jaha.113.000439

[46]

10.1016/j.ejphar.2021.174260

[47]

10.1152/ajpheart.01032.2008

[48]

10.1152/ajpheart.00587.2006

[49]

10.1089/ars.2012.4550

[50]

10.1016/j.taap.2023.116412

Showing 50 of 52 references

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Details

Published: Mar 10, 2025
Vol/Issue: 182(12)
Pages: 2772-2789
License: View

Authors

H

Hong‐Xia Guo

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

R

Run‐Nan Tantai

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

B

Bin Yang

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

L

Li‐Guo Yang

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China; Shanxi Provincial People's Hospital Taiyuan China

Y

Yuan Ma

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

H

Hui‐Ping Zhao

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

J

Jing Wang

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

X

Xiao‐Juan Zhang

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China; Shanxi Province Cardiovascular Hospital Taiyuan China

R

Rui‐Hua Wang

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

F

Fei Wang

Shanxi Province Cardiovascular Hospital Taiyuan China

J

Jia‐Pu Wang

Shanxi Province Cardiovascular Hospital Taiyuan China

R

Rui‐Fang Chi

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

F

Fu‐Zhong Qin

The Second Hospital of Shanxi Medical University Taiyuan China; Shanxi Medical University Taiyuan China

Y

Ya‐Xin Liu

Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Funding

National Natural Science Foundation of China Award: 81441014

Natural Science Foundation of Shanxi Province Award: 202203021211055

Cite This Article

Hong‐Xia Guo, Run‐Nan Tantai, Bin Yang, et al. (2025). SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines. British Journal of Pharmacology, 182(12), 2772-2789. https://doi.org/10.1111/bph.70005

SEW2871 attenuates myocyte necroptosis in heart failure through inhibition of oxidative stress and inflammatory cytokines

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