Age- and sex-dependent gene expression landscapes in dyslipidaemia-driven atherosclerosis

Age- and sex-dependent gene expression landscapes in dyslipidaemia-driven atherosclerosis | 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 Short Report Age- and sex-dependent gene expression landscapes in dyslipidaemia-driven atherosclerosis Pietro Hiram Guzzi, Elisabetta Pedace, Pierangelo Veltri This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8358462/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 Ageing and biological sex are major determinants of cardiometabolic risk, yet their combined impact on the molecular regulation of dyslipidaemiaassociated atherosclerosis remains incompletely understood. Here, we present an integrative bioinformatic analysis to investigate age- and sexdependent gene expression patterns across tissues relevant to vascular disease. Using curated disease–gene associations from the T2DiACoD database, tissue-specific transcriptomic data from GTEx, and networklevel information from STRING, we identify genes exhibiting monotonic age-related changes in basal expression in blood, tibial artery and aortic tissues. In tibial artery tissue, multiple genes involved in lipid metabolism, inflammatory signalling and vascular remodelling show age-associated expression changes, forming a connected protein–protein interaction network. Additional tissue-specific effects are observed for KLF14 in blood and TCF7L2 in aortic tissue. Sex-dependent expression differences are detected for a subset of age-modulated genes, highlighting the importance of incorporating sex as a biological variable. While exploratory, these findings suggest that ageing and sex shape coordinated transcriptional programmes in vascular tissues and provide candidate molecular signatures for further investigation into dyslipidaemia-related atherosclerosis Full Text Additional Declarations The authors declare no competing interests. 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8358462","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":560063209,"identity":"1e2f801d-b78e-4a69-a4ec-ff7a94dfc8a1","order_by":0,"name":"Pietro Hiram Guzzi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArklEQVRIiWNgGAWjYBACAwhpw8DAjOASpSUNpoUIPVAlh9H4+IA5/xrjjz8KziduZ2d+/IGh4A9hLZYz3hgYSBjcTtzZzAZ0FVEOu3HGIMEAqGXDYR6GBKK1HEgwOAfWcoA4Led7DBsOGBwAaWFsINIWtmLGBoNk4w2H2YwZEgyMibHl8OaPP/7YyW44f/jxhw9/5AhrYZBIQOIk4FCECvgPEKVsFIyCUTAKRjIAALx3OC2pERg3AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5542-2997","institution":"Department of Surgical and Medical Sciences, University of Catanzaro","correspondingAuthor":true,"prefix":"","firstName":"Pietro","middleName":"Hiram","lastName":"Guzzi","suffix":""},{"id":560063210,"identity":"b205b314-b268-4a0e-af96-5f3bb5ce8090","order_by":1,"name":"Elisabetta Pedace","email":"","orcid":"","institution":"ASP Catanzaro","correspondingAuthor":false,"prefix":"","firstName":"Elisabetta","middleName":"","lastName":"Pedace","suffix":""},{"id":560063211,"identity":"6267e456-9dd1-45aa-a0a4-365ac30c1d5d","order_by":2,"name":"Pierangelo Veltri","email":"","orcid":"https://orcid.org/0000-0003-2494-0294","institution":"DIMES, University of Calabria","correspondingAuthor":false,"prefix":"","firstName":"Pierangelo","middleName":"","lastName":"Veltri","suffix":""}],"badges":[],"createdAt":"2025-12-14 14:01:50","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8358462/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8358462/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98435834,"identity":"995aeb67-1615-4027-8a5c-fac4dec5900b","added_by":"auto","created_at":"2025-12-17 16:54:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1478860,"visible":true,"origin":"","legend":"","description":"","filename":"preprints86971manuscript1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8358462/v1_covered_819b1385-82ef-48b6-82cd-c3d7258548ac.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eAge- and sex-dependent gene expression landscapes in dyslipidaemia-driven atherosclerosis\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Magna Graecia University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8358462/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8358462/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAgeing and biological sex are major determinants of cardiometabolic risk, yet their combined impact on the molecular regulation of dyslipidaemiaassociated atherosclerosis remains incompletely understood. Here, we present an integrative bioinformatic analysis to investigate age- and sexdependent gene expression patterns across tissues relevant to vascular disease. Using curated disease–gene associations from the T2DiACoD database, tissue-specific transcriptomic data from GTEx, and networklevel information from STRING, we identify genes exhibiting monotonic age-related changes in basal expression in blood, tibial artery and aortic tissues. In tibial artery tissue, multiple genes involved in lipid metabolism, inflammatory signalling and vascular remodelling show age-associated expression changes, forming a connected protein–protein interaction network. Additional tissue-specific effects are observed for KLF14 in blood and TCF7L2 in aortic tissue. Sex-dependent expression differences are detected for a subset of age-modulated genes, highlighting the importance of incorporating sex as a biological variable. 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