HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression

HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression | 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 Brief Communication HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression Celestine Wanjalla, Laventa Obare, Samuel Bailin, Xiuqi Zhang, and 48 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5125826/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Chronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between ABCA1 and CXCL12 gene expressions with atherosclerosis, partly influenced by HIV. Biological sciences/Immunology/Inflammation/Chronic inflammation Biological sciences/Immunology/Infectious diseases/HIV infections Health sciences/Medical research/Translational research Atherosclerosis cardiovascular disease HIV CD163 CXCL12 ABCA1 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 9.20.2024CoronaryarteryPaperSupplementalTablesandFiguresFinal.pdf Suplemental Figures and Tables 9.14.24CoronaryPlaqueHIVPaperWanjallaBioVUSupplementalTablesFinal.xlsx Supplemental Tables Cite Share Download PDF Status: Under Review 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-5125826","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Brief Communication","associatedPublications":[],"authors":[{"id":359903413,"identity":"8015e824-67c3-494d-9b24-3b4052c9f0e8","order_by":0,"name":"Celestine 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The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between ABCA1 and CXCL12 gene expressions with atherosclerosis, partly influenced by HIV.","manuscriptTitle":"HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-18 05:57:26","doi":"10.21203/rs.3.rs-5125826/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bb3b9625-84df-409d-aa3d-983a53f41bab","owner":[],"postedDate":"October 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":38300983,"name":"Biological sciences/Immunology/Inflammation/Chronic inflammation"},{"id":38300984,"name":"Biological sciences/Immunology/Infectious diseases/HIV infections"},{"id":38300985,"name":"Health sciences/Medical research/Translational research"}],"tags":[],"updatedAt":"2024-10-18T05:57:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-18 05:57:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5125826","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5125826","identity":"rs-5125826","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}