Post-treatment with Resolvin D1 attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition

Xinyu Li; 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

Biomedicine & Pharmacotherapy (Aug 2024)

Post-treatment with Resolvin D1 attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition

Xinyu Li,
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

Affiliations

Xinyu Li: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Hui Li: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Bo Feng: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Xiaoyan Chen: Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Ting Chen: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Jiafei Lu: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Huating Xie: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Nana Su: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Houlin Chen: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Chenghao Lou: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Runxin Zhuang: Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Xi Chen: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China
Shengwei Jin: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China; Corresponding authors at: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Lucheng District, Wenzhou, Zhejiang 325027, China.
Yu Hao: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou 325000, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou 325000, China; Corresponding authors at: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Lucheng District, Wenzhou, Zhejiang 325027, China.

Journal volume & issue: Vol. 177
p. 117023

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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