Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function.

IF 1.6 4区医学 Q2 MEDICINE, GENERAL & INTERNAL Open Medicine Pub Date : 2025-02-06 eCollection Date: 2025-01-01 DOI:10.1515/med-2024-1137

Ruifeng Bai, Xinyang Yue, Xuan Tian, Huiru Zhao, Ying Liu, Tian Li, Jun Wu

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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.

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溶血磷脂酸2通过保护内皮屏障功能减轻深静脉血栓形成。

背景：溶血磷脂酸2 （LPA2）在深静脉血栓形成（DVT）中的具体作用尚不清楚。方法：以野生型（WT）和LPA2全基因敲除（LPA2 -/-）小鼠为模型，建立下腔静脉环回缩模型。我们检查了DVT的发生率、血栓湿重、血栓长度，通过Evans蓝染色法评估了体内内皮细胞的通透性、细胞活力和小鼠下腔静脉内皮细胞（EC）的通透性。采用蛋白质组学、组织病理学、免疫组化、western blotting等方法研究LPA2在DVT中的作用。结果：Lpar2缺乏可增加血管内皮通透性，促进DVT的进展。组织学检查显示Lpar2 -/- DVT小鼠血栓炎症加重。在体外，Lpar2 -/-导致内皮细胞通透性增加。蛋白质组学结果表明Lpar2 -/-后DVT可能与紧密连接（TJ）蛋白有关。LPA2激动剂2-[4-（1,3-二氧基- 1h， 3h -苯并异喹啉-2-基）丁基磺胺酰]苯甲酸显著降低血管内皮通透性，增加血管内皮TJ蛋白occludens-1的表达。结论：这些数据为LPA2在DVT中内皮屏障保护提供了一种新的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Open Medicine Medicine-General Medicine

CiteScore

3.00

自引率

0.00%

发文量

153

审稿时长

20 weeks

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.