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Abdominal aortic aneurysm (AAA) is a disease characterized by deleterious remodelling of the aortic wall, increasing the risk of rupture and sudden death. Although succinate has been linked to vascular diseases, its regulation within the aorta and potential involvement in AAA remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims and Results<\/jats:title>\n                    <jats:p>In this study, we combined analyses of human plasma and aortic tissue with cell culture experiments to help understand the role of succinate in AAA pathogenesis. Analysis of plasma samples from 461 AAA patients and 189 age\u2010matched controls (67\u201372\u2009years) from the \u2018Viborg Vascular Screening Trial\u2019 showed significantly increased succinate levels in AAA individuals, approximately 28% higher than in controls. Logistic regression adjusted for cardiovascular risk factors confirmed a strong association (OR\u2009=\u20094.56; 95% CI: 2.57\u20138.09, highest vs. lowest tertile). Analysis of tissue homogenates confirmed elevated succinate levels in AAA compared to control aortic tissue. Transcriptomic analyses of public AAA datasets indicated that succinate accumulation may result from downregulation of the succinate dehydrogenase complex and upregulation of the gamma\u2010aminobutyric acid shunt pathway, particularly in vascular smooth muscle cells (VSMCs). In cultures, we showed that dedifferentiation increases succinate production, while succinate treatment, in turn, promotes VSMC dedifferentiation in a process involving HIF1\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study proposes succinate as a driver of AAA through a feed\u2010forward loop involving HIF1\u03b1 signalling and VSMC phenotypic switching. Our work identifies the succinate\u2013HIF1\u03b1 axis as a promising therapeutic target to disrupt key pathological processes underlying AAA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70170","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:06:31Z","timestamp":1769774791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a pathological feed\u2010forward loop linking succinate, HIF1\u03b1 signalling and vascular remodelling in abdominal aortic aneurysm"],"prefix":"10.1111","volume":"56","author":[{"given":"S.","family":"Griepke","sequence":"first","affiliation":[{"name":"Cardiovascular and Renal Research Unit, Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. L.","family":"Tripodi","sequence":"additional","affiliation":[{"name":"Cardiovascular and Renal Research Unit, Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. L.","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics, and Biodemography, Department of Public Health University of Southern Denmark  Odense Denmark"},{"name":"Department of Cardiac, Thoracic and Vascular Surgery Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Cardiovascular and Renal Research Unit, Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology Odense University Hospital  Odense Denmark"},{"name":"Elite Research Centre for Individualized Medicine in Arterial Diseases (CIMA) Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. M.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology Odense University Hospital  Odense Denmark"},{"name":"Elite Research Centre for Individualized Medicine in Arterial Diseases (CIMA) Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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