Lymphangiogenesis in Abdominal Aortic Aneurysm regulates the balance between resident and circulating eosinophils via a 15-lipoxygenase-dependent mechanism

Lymphangiogenesis in Abdominal Aortic Aneurysm regulates the balance between resident and circulating eosinophils via a 15-lipoxygenase-dependent mechanism | 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 Lymphangiogenesis in Abdominal Aortic Aneurysm regulates the balance between resident and circulating eosinophils via a 15-lipoxygenase-dependent mechanism Barbara Garmy-Susini, Aurelien Hostalrich, Lena Verdu, Elisa Balzan, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8403451/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 The abdominal aortic aneurysm (AAA) is a chronic degeneration of the aortic wall involving an inflammatory response, aberrant remodeling of the extracellular matrix, and the development of microvessels. Among these, lymphatic capillaries develop in the adventitia. However, the role of lymphangiogenesis in AAA remains unclear. Here, we confirmed the development of lymphatic vessels in both human and mouse AAA. This was associated with a decrease in specialized pro-resolving mediators (SPM) generated by 15-Lipoxygenase (15LO), an enzyme that controls resolution of inflammation in lymphatic diseases. Lymphatic selective depletion of 15LO (Prox1cre; Alox15fl/fl mice) increased both systemic and resident eosinophil (EOS) accumulation in lesions, but had no effect on other immune cell populations. Mechanistically, in vitro depletion of 15LO in lymphatic endothelial cells (LEC) significantly decreased EOS adhesion. In contrast, 15LO LEC depletion improved transendothelial migration. In vivo, the rescue of 15LO using lentivector transduction modified the balance between resident and systemic EOS in favor of the resident ones and reduced the AAA lesion. Altogether, we show that lymphatic vessels play a protective role in AAA by regulating the trafficking of EOS into the aorta wall. Health sciences/Diseases/Cardiovascular diseases/Vascular diseases/Aneurysm Health sciences/Diseases/Cardiovascular diseases/Vascular diseases/Aortic diseases Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Hostalrichsupplementalinformations.pdf Supplementary figures and legends 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. 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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-8403451","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":573818756,"identity":"0276b9cf-33ae-4e1a-a319-b63e45de9948","order_by":0,"name":"Barbara 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Among these, lymphatic capillaries develop in the adventitia. However, the role of lymphangiogenesis in AAA remains unclear.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHere, we confirmed the development of lymphatic vessels in both human and mouse AAA. This was associated with a decrease in specialized pro-resolving mediators (SPM) generated by 15-Lipoxygenase (15LO), an enzyme that controls resolution of inflammation in lymphatic diseases. Lymphatic selective depletion of 15LO (Prox1cre; Alox15fl/fl mice) increased both systemic and resident eosinophil (EOS) accumulation in lesions, but had no effect on other immune cell populations. Mechanistically, in vitro depletion of 15LO in lymphatic endothelial cells (LEC) significantly decreased EOS adhesion. In contrast, 15LO LEC depletion improved transendothelial migration. 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