Xinyu Lia, Hui Li, Bo Feng, Xiaoyan Chen, Ting Chen, Jiafei Lu, Huating Xie, Nana Su, Houlin Chen, Chenghao Lou, Runxin Zhuang, Xi Chen, Shengwei Jin, Yu Hao
Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University. Ruijin Hospital and Shanghai Jiao Tong University School of Medicine.
China
Biomedicine and Pharmacotherapy
Biomed Pharmacother 2024;
DOI: 10.1016/j.biopha.2024.117023
Abstract
Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is an important manifestation and mechanism of pulmonary vascular remodeling. Resolvin D1 (RvD1) is an endogenous lipid mediator promoting the resolution of inflammation. However, the role of RvD1 on EndMT in PH remains unknown. Here, we aimed to investigate the effect and mechanisms of RvD1 on the treatment of PH. We showed that RvD1 and its receptor FPR2 expression were markedly decreased in PH patients and both chronic hypoxia-induced PH (CH-PH) and sugen 5416/hypoxia-induced PH (SuHx-PH) mice models. RvD1 treatment decreased right ventricular systolic pressure (RVSP) and alleviated right ventricular function, and reduced pulmonary vascular remodeling and collagen deposition in the perivascular of both two PH mice models. Then, RvD1 inhibited EndMT in both the lungs of PH mice models and primary cultured human umbilical vein endothelial cells (HUVECs) treated with TGF-β and IL-1β. Moreover, RvD1 inhibited EndMT by downregulating Smad2/3 phosphorylation in vivo and in vitro via FPR2. In conclusion, our date suggest that RvD1/FPR2 axis prevent experimental PH by inhibiting endothelial-mensenchymal-transition and may be a therapeutic target for PH.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Medical Therapy. Efficacy or Lack of Efficacy
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes