Ruoyu Wang MM , Yue Zeng MM , Ziqi Chen PhD , Dongwei Ma MM , Xiaozhe Zhang PhD , Guifu Wu MD, PhD , Wendong Fan PhD
{"title":"剪切敏感性 circRNA-LONP2 通过靶向 NRF2/HO1 信号促进内皮炎症和动脉粥样硬化","authors":"Ruoyu Wang MM , Yue Zeng MM , Ziqi Chen PhD , Dongwei Ma MM , Xiaozhe Zhang PhD , Guifu Wu MD, PhD , Wendong Fan PhD","doi":"10.1016/j.jacbts.2024.02.019","DOIUrl":null,"url":null,"abstract":"<div><p>Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p–mediated nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001013/pdfft?md5=40566b453eaf52a13c53e7ce20a89fba&pid=1-s2.0-S2452302X24001013-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Shear-Sensitive circRNA-LONP2 Promotes Endothelial Inflammation and Atherosclerosis by Targeting NRF2/HO1 Signaling\",\"authors\":\"Ruoyu Wang MM , Yue Zeng MM , Ziqi Chen PhD , Dongwei Ma MM , Xiaozhe Zhang PhD , Guifu Wu MD, PhD , Wendong Fan PhD\",\"doi\":\"10.1016/j.jacbts.2024.02.019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p–mediated nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.</p></div>\",\"PeriodicalId\":14831,\"journal\":{\"name\":\"JACC: Basic to Translational Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2452302X24001013/pdfft?md5=40566b453eaf52a13c53e7ce20a89fba&pid=1-s2.0-S2452302X24001013-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC: Basic to Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2452302X24001013\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452302X24001013","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Shear-Sensitive circRNA-LONP2 Promotes Endothelial Inflammation and Atherosclerosis by Targeting NRF2/HO1 Signaling
Hemodynamic shear stress is a frictional force that acts on vascular endothelial cells and is essential for endothelial homeostasis. Physiological laminar shear stress (LSS) suppresses endothelial inflammation and protects arteries from atherosclerosis. Herein, we screened differentially expressed circular RNAs (circRNAs) that were significantly altered in LSS-stimulated endothelial cells and found that circRNA-LONP2 was involved in modulating the flow-dependent inflammatory response. Furthermore, endothelial circRNA-LONP2 overexpression promoted endothelial inflammation and atherosclerosis in vitro and in vivo. Mechanistically, circRNA-LONP2 competitively sponged miR-200a-3p and subsequently promoted Kelch-like ECH-associated protein 1, Yes-associated protein 1, and enhancer of zeste homolog 2 expression, thereby inactivating nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling, promoting oxidative stress and endothelial inflammation, and accelerating atherosclerosis. LSS-induced down-regulation of circRNA-LONP2 suppresses endothelial inflammation, at least in part, by activating the miR-200a-3p–mediated nuclear factor erythroid 2–related factor 2/heme oxygenase-1 signaling pathway. CircRNA-LONP2 may serve as a new therapeutic target for atherosclerosis.
期刊介绍:
JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.