Maresin 1 intervention reverses experimental pulmonary arterial hypertension in mice

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

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)5132-5147
JournalBritish Journal of Pharmacology
Issue number22
Early online date28 Jun 2022
Publication statusE-pub ahead of print - 28 Jun 2022

Bibliographical note

Funding Information:
The authors thank Professor Ming Li for technical assistance in our experiment. This work was supported in part by the grants from Wenzhou Major Science and Technology Innovation Project (2018ZY006), Clinical Research Foundation of the 2nd Affiliated Hospital of Wenzhou Medical University (SAHoWMU‐CR2018‐11‐134), the Key R&D Program of Zhejiang Province (2019C03011), the Natural Science Foundation of Zhejiang Province (LQ20H150003), and the Wenzhou Science and Technology Bureau Project (Y20190118).

Publisher Copyright:
© 2022 British Pharmacological Society.


  • Maresin 1
  • pulmonary arterial hypertension
  • pulmonary vascular remodelling
  • right ventricular dysfunction

ASJC Scopus subject areas

  • Pharmacology


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