Rhodioloside attenuated atherosclerosis progression by inhibiting VCAM-1 gene transcription mediated by p65 activation and CSN5 deubiquitination in endothelial cells

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The paper investigated whether rhodioloside could attenuate atherosclerosis progression by modulating inflammatory adhesion pathways in ApoE−/− mice fed a high-fat diet, assessing protein expression in aortic endothelial tissue. Rhodioloside reduced aortic endothelial levels of GATA2, CSN5, and VCAM-1 and decreased phosphorylation of the NF-κB p65 subunit, alongside effects on ubiquitination and protein-protein interactions involving PP2Ac and I2PP2A. The authors report that rhodioloside directly suppressed p65-driven transcriptional activity by targeting the I2PP2A–PP2Ac axis, but the work is presented as a preprint that has not undergone peer review. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Monocyte-endothelial cell adhesion played a pivotal role in the initial stages of Atherosclerosis (AS) progression, exacerbating lipid disturbance and worsening the condition. Rhodioloside (Rho), a renowned compound in traditional Chinese medicine, possesses diverse pharmacological attributes, including anti-inflammatory, antioxidant, anticancer, anti-metabolic dysregulation, and neuroprotective properties. However, the exact mechanism by which Rho exerts its anti-AS effect is still not fully understood. This study aimed to investigate the potential therapeutic benefits of Rho in combating AS. ApoE−/− mice were fed with a High Fat Diet (HFD) and administered Rho treatment. The investigation evaluated the expression levels of GATA2, CSN5, and VCAM-1 proteins in the endothelium of the aorta. The findings revealed that Rho treatment led to a reduction in the protein expression of GATA2, CSN5, and VCAM-1 in the aortic endothelium, accompanied by decreased phosphorylation of p65. Furthermore, Rho inhibited the ubiquitination of GATA2 and weakened the interaction between PP2Ac and I2PP2A. Additionally, Rho directly suppressed the transcriptional activity of the NF-κB subunit p65 by targeting the I2PP2A-PP2Ac axis.
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Rhodioloside attenuated atherosclerosis progression by inhibiting VCAM-1 gene transcription mediated by p65 activation and CSN5 deubiquitination in endothelial cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Rhodioloside attenuated atherosclerosis progression by inhibiting VCAM-1 gene transcription mediated by p65 activation and CSN5 deubiquitination in endothelial cells Jing Ji, Wenlian Tang, Xingquan Liu, Lin Luo, Xin Xin, Nana Ju, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4633753/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Monocyte-endothelial cell adhesion played a pivotal role in the initial stages of Atherosclerosis (AS) progression, exacerbating lipid disturbance and worsening the condition. Rhodioloside (Rho), a renowned compound in traditional Chinese medicine, possesses diverse pharmacological attributes, including anti-inflammatory, antioxidant, anticancer, anti-metabolic dysregulation, and neuroprotective properties. However, the exact mechanism by which Rho exerts its anti-AS effect is still not fully understood. This study aimed to investigate the potential therapeutic benefits of Rho in combating AS. ApoE −/− mice were fed with a High Fat Diet (HFD) and administered Rho treatment. The investigation evaluated the expression levels of GATA2, CSN5, and VCAM-1 proteins in the endothelium of the aorta. The findings revealed that Rho treatment led to a reduction in the protein expression of GATA2, CSN5, and VCAM-1 in the aortic endothelium, accompanied by decreased phosphorylation of p65. Furthermore, Rho inhibited the ubiquitination of GATA2 and weakened the interaction between PP2Ac and I2PP2A. Additionally, Rho directly suppressed the transcriptional activity of the NF-κB subunit p65 by targeting the I2PP2A-PP2Ac axis. Atherosclerosis Rhodioloside Monocyte-endothelial cell adhesion TNF-α VCAM-1 PP2Ac Full Text Additional Declarations No competing interests reported. Supplementary Files highlights.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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