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.
Bibliographical noteFunding 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).
© 2022 British Pharmacological Society.
- Maresin 1
- pulmonary arterial hypertension
- pulmonary vascular remodelling
- right ventricular dysfunction
ASJC Scopus subject areas