Department of Anaesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, China.
Br J Pharmacol. 2022 Nov;179(22):5132-5147. doi: 10.1111/bph.15906. Epub 2022 Aug 9.
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.
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.
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.
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.
肺动脉高压（PAH）是一种肺血管阻塞性疾病，可导致右心衰竭和死亡。maresin 1 是一种内源性脂质介质，已知可促进炎症消退。然而，maresin 1 对 PAH 的影响尚不清楚。
采用 UPLC 测定血清maresin 1 浓度。通过联合给予苏金 5416 注射和缺氧暴露建立 PAH 小鼠模型。maresin 1 治疗后，通过血流动力学测量和超声心动图分别测量右心室收缩压（RVSP）和右心室功能。通过组织学染色评估血管重塑。共聚焦显微镜和 Western blot 用于检测相关蛋白表达。在原代大鼠肺动脉平滑肌细胞（PASMCs）中进行细胞迁移、增殖和凋亡检测。Western blot 和 siRNA 转染用于阐明maresin 1 的作用机制。
PAH 患者和小鼠的内源性血清maresin 1 降低。maresin 1 治疗可降低 PAH 小鼠的 RVSP 并改善右心室功能障碍（RVD）。maresin 1 逆转了肺血管重塑的异常变化，减轻了内皮向间充质转化并增强了α-SMA 阳性细胞的凋亡。此外，maresin 1 通过 LGR6 抑制 STAT、AKT、ERK 和 FoxO1 磷酸化，抑制 PASMC 增殖并促进凋亡。
maresin 1 改善了 PAH 小鼠异常的肺血管重塑和右心室功能障碍，靶向异常的 PASMC 增殖。这表明maresin 1 可能对血管疾病具有潜在的治疗作用。
