Epicardial fat drives macrophage response in atrial cardiomyopathy | 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 Article Epicardial fat drives macrophage response in atrial cardiomyopathy Nadine Suffee, Laure Crepin, Mougenot Nathalie, Eva Trenquier, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6455438/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 Inflammation is associated with atrial fibrillation (AF), but its precise impact on the long-term progression of AF substrate, also called atrial cardiomyopathy (ACM), remains debated. Here, using spatial gene expression analysis, macrophage subpopulations mainly confined to the epicardial fat depots were identified in human atria. In a mouse model of obesity and ACM, macrophage recruitment was associated with atrial adiposity. Single-cell RNA sequencing identified Lyve1+ resident and CCR2+ monocyte-derived macrophages in obese mouse atria. In obese mice, depleting Lyve1+ macrophages prevented early fat expansion and caused myocardial dystrophy, while CCR2+ macrophage depletion prevented fatty-fibrotic remodeling, atrial dilation, and AF. These data highlighted the pivotal role of epicardial adipose tissue in macrophage activation during ACM development and identified Lyve1+ macrophages as key regulators of atrial adiposity. Biological sciences/Physiology/Cardiovascular biology/Cardiovascular diseases/Cardiomyopathies Biological sciences/Immunology/Inflammation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations There is NO Competing Interest. ethics approval: Service de la performance, du financement et de la contractualisation avec les organismes de recherche Département des pratiques de recherche réglementées Cellule Animaux utilisés à des Fins Scientifiques - AFiS for mouse #35565 for human specimen DC-2019-3798 and DC-2020-4183 Supplementary Files TableSupplemental.pdf Supplemantal Table SupFiguresS1S26.pdf Supplemantal Figures 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. 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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-6455438","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":444431123,"identity":"ce8456bf-8339-4ed9-944d-3f3da53890db","order_by":0,"name":"Nadine 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