Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

IF 1.5 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Clinical and Experimental Hypertension Pub Date : 2024-12-31 Epub Date: 2024-03-25 DOI:10.1080/10641963.2024.2332695

Xinyu Deng, Hao Luo, Jing He, Wang Deng, Daoxin Wang

{"title":"Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.","authors":"Xinyu Deng, Hao Luo, Jing He, Wang Deng, Daoxin Wang","doi":"10.1080/10641963.2024.2332695","DOIUrl":null,"url":null,"abstract":"Background: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear.Methods: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography.Results: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'‑adenosine monophosphate‑activated protein kinase (p‑AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C).Conclusions: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"46 1","pages":"2332695"},"PeriodicalIF":1.5000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Hypertension","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10641963.2024.2332695","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear.

Methods: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography.

Results: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'‑adenosine monophosphate‑activated protein kinase (p‑AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C).

Conclusions: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

查看原文本刊更多论文

网膜素-1通过AMPKα信号传导抑制内质网应激，从而改善肺动脉高压。

背景：肺动脉内皮功能障碍是缺氧诱发肺动脉高压（PAH）的原因之一。网织蛋白-1作为一种新型脂肪细胞因子，对心血管疾病具有重要的保护作用。然而，网织蛋白-1对PAH的作用和内在机制仍不清楚：方法：通过低氧室诱导 SD（Sprague & Dawley）大鼠患 PAH 4 周。使用 PowerLab 数据采集系统进行血液动力学评估，并用苏木精和伊红（H&E）染色进行组织病理学分析。用线肌电图评估肺动脉内皮功能：结果：我们发现奥门冬酰胺-1能明显改善缺氧大鼠的肺内皮功能，并减轻 PAH。从机理上讲，我们发现奥门冬酰胺-1能提高5'-腺苷酸单磷酸磷酸化蛋白激酶（p-AMPK）水平，降低内质网（ER）应激，增加缺氧大鼠肺动脉中NO的生成。然而，用 AMPK 抑制剂（化合物 C）处理后，奥门冬酰胺-1 的作用被取消：我们的研究结果揭示了网苔素-1通过AMPKα信号传导抑制ER应激对PAH的保护作用，为治疗PAH提供了一种具有转化潜力的药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical and Experimental Hypertension 医学-外周血管病

CiteScore

3.90

自引率

0.80%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.