Ruifeng Bai, Xinyang Yue, Xuan Tian, Huiru Zhao, Ying Liu, Tian Li, Jun Wu
{"title":"Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function.","authors":"Ruifeng Bai, Xinyang Yue, Xuan Tian, Huiru Zhao, Ying Liu, Tian Li, Jun Wu","doi":"10.1515/med-2024-1137","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The specific role of lysophosphatidic acid 2 (LPA<sub>2</sub>) in deep vein thrombosis (DVT) remains unclear.</p><p><strong>Methods: </strong>An inferior vena cava annulus retraction model of DVT was established in wild-type (WT) and global LPA<sub>2</sub> knockout (<i>Lpar2</i> <sup><i>-/-</i></sup> ) mice. We examined the incidence of DVT, wet weight of thrombus, length of thrombus, assessed endothelial permeability through Evans blue dye assay <i>in vivo,</i> cell viability, and endothelial cell (EC) permeability of mouse inferior vena cava ECs <i>in vitro.</i> Proteomics, histopathology, immunohistochemistry, and western blotting were employed to investigate the role of LPA<sub>2</sub> in DVT.</p><p><strong>Results: </strong><i>Lpar2</i> deficiency increased vascular endothelial permeability and promoted the progression of DVT. Histological examination revealed aggravated inflammation in the thrombus of <i>Lpar2</i> <sup>-/-</sup> DVT mice. <i>In vitro</i>, <i>Lpar2</i> <sup>-/-</sup> resulted in increased permeability of ECs. Proteomic results indicated that DVT after <i>Lpar2</i> <sup>-/-</sup> may be related to tight junction (TJ) protein. LPA<sub>2</sub> agonist, 2-[4-(1,3-dioxo-1<i>H</i>,3<i>H</i>-benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid, significantly reduced vascular endothelial permeability as well as increased expression of the vascular endothelial TJ protein zonula occludens-1.</p><p><strong>Conclusion: </strong>These data provide a novel mechanism of endothelial barrier protection of LPA<sub>2</sub> in DVT.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20241137"},"PeriodicalIF":1.7000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806235/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/med-2024-1137","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The specific role of lysophosphatidic acid 2 (LPA2) in deep vein thrombosis (DVT) remains unclear.
Methods: An inferior vena cava annulus retraction model of DVT was established in wild-type (WT) and global LPA2 knockout (Lpar2-/- ) mice. We examined the incidence of DVT, wet weight of thrombus, length of thrombus, assessed endothelial permeability through Evans blue dye assay in vivo, cell viability, and endothelial cell (EC) permeability of mouse inferior vena cava ECs in vitro. Proteomics, histopathology, immunohistochemistry, and western blotting were employed to investigate the role of LPA2 in DVT.
Results: Lpar2 deficiency increased vascular endothelial permeability and promoted the progression of DVT. Histological examination revealed aggravated inflammation in the thrombus of Lpar2-/- DVT mice. In vitro, Lpar2-/- resulted in increased permeability of ECs. Proteomic results indicated that DVT after Lpar2-/- may be related to tight junction (TJ) protein. LPA2 agonist, 2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid, significantly reduced vascular endothelial permeability as well as increased expression of the vascular endothelial TJ protein zonula occludens-1.
Conclusion: These data provide a novel mechanism of endothelial barrier protection of LPA2 in DVT.
期刊介绍:
Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.