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. 2022 Nov;179(22):5132-5147.
doi: 10.1111/bph.15906. Epub 2022 Aug 9.

Maresin 1 intervention reverses experimental pulmonary arterial hypertension in mice

Hui Li  1 , Xinyu Li  1 , Yu Hao  1 , Chenghua Wu  1 , Yuhao Fu  1 , Nana Su  1 , Houlin Chen  1 , Binyu Ying  1 , Haixing Wang  1 , Lihuang Su  2 , Haijian Cai  2 , Qinlian He  2 , Mengsi Cai  2 , Junwei Sun  2 , Jing Lin  3 , Aaron Scott  4   5 , Fanggao Smith  1   4   5 , Xiaoying Huang  2 , Shengwei Jin  1
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Free article

Maresin 1 intervention reverses experimental pulmonary arterial hypertension in mice

Hui Li et al. Br J Pharmacol. 2022 Nov.
Free article

Abstract

Background and purpose: Pulmonary arterial hypertension (PAH) is a pulmonary vasculature obstructive disease that leads to right heart failure and death. Maresin 1 is an endogenous lipid mediator known to promote inflammation resolution. However, the effect of Maresin 1 on PAH remains unclear.

Experimental approach: The serum Maresin 1 concentration was assessed using UPLC. A mouse model of PAH was established by combining the Sugen 5416 injection and hypoxia exposure. After treatment with Maresin 1, the right ventricular systolic pressure (RVSP) and right ventricular function were measured by haemodynamic measurement and echocardiography, respectively. Vascular remodelling was evaluated by histological staining. Confocal microscopy and western blot were used to test related protein expression. In vitro cell migration, proliferation and apoptosis assays were performed in primary rat pulmonary artery smooth muscle cells (PASMCs). Western blotting and siRNA transfection were used to clarify the mechanism of Maresin 1.

Key results: Endogenous serum Maresin 1 was decreased in PAH patients and mice. Maresin 1 treatment decreased RVSP and attenuated right ventricular dysfunction (RVD) in the murine PAH model. Maresin 1 reversed abnormal changes in pulmonary vascular remodelling, attenuating endothelial to mesenchymal transformation and enhancing apoptosis of α-SMA positive cells. Furthermore, Maresin 1 inhibited PASMC proliferation and promoted apoptosis by inhibiting STAT, AKT, ERK, and FoxO1 phosphorylation via LGR6.

Conclusion and implications: Maresin 1 improved abnormal pulmonary vascular remodelling and right ventricular dysfunction in PAH mice, targeting aberrant PASMC proliferation. This suggests Maresin 1 may have a potent therapeutic effect in vascular disease.

Keywords: Maresin 1; pulmonary arterial hypertension; pulmonary vascular remodelling; right ventricular dysfunction.

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References

REFERENCES

    1. Albuquerque-Souza, E., Schulte, F., Chen, T., Hardt, M., Hasturk, H., van Dyke, T. E., Holzhausen, M., & Kantarci, A. (2020). Maresin-1 and Resolvin E1 promote regenerative properties of periodontal ligament stem cells under inflammatory conditions. Frontiers in Immunology, 11, 585530. https://doi.org/10.3389/fimmu.2020.585530
    1. Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., … Ye, R. D. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. British Journal of Pharmacology, 178(S1), S27-S156. https://doi.org/10.1111/bph.15538
    1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., … Waldman, S. A. (2021a). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Catalytic receptors. British Journal of Pharmacology, 178(S1), S264-S312. https://doi.org/10.1111/bph.15541
    1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Boison, D., Burns, K. E., Dessauer, C., Gertsch, J., Helsby, N. A., Izzo, A. A., Koesling, D., … Wong, S. S. (2021b). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. British Journal of Pharmacology, 178(S1), S313-S411. https://doi.org/10.1111/bph.15542
    1. Alexander, S. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Buneman, O. P., Cidlowski, J. A., Christopoulos, A., Davenport, A. P., Collaborators, C. G. T. P., Fabbro, D., Spedding, M., Striessnig, J., Davies, J. A., … Zolghadri, Y. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Introduction and Other Protein Targets. British Journal of Pharmacology, 178(S1), S1-S26. https://doi.org/10.1111/bph.15537

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