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The study investigates leptin, a hormone elevated in obesity, and finds that hyperleptinemia is common in TAD patients, suggesting its role in disease pathogenesis. Using leptin\u2010knockout mice, it is demonstrated that exogenous leptin exacerbates TAD by promoting phenotypic transitions in vascular smooth muscle cells (VSMCs). These adverse effects are reversible with pharmacologic leptin blockade, indicating potential therapeutic benefits. Single\u2010cell RNA sequencing reveals a novel smooth muscle cells (SMC) cluster, Nrip2\n                    <jats:sup>+<\/jats:sup>\n                    , in the aorta, with a distinct contractile gene profile. Increased Nrip2\n                    <jats:sup>+<\/jats:sup>\n                    VSMCs are linked to enhanced mitochondrial energy metabolism. Elevated Nrip2\n                    <jats:sup>+<\/jats:sup>\n                    VSMCs inhibit the leptin\u2010induced transition from a contractile to a synthetic phenotype, reducing TAD incidence. The findings suggest that high blood leptin levels contribute to the increased TAD risk in obese individuals by suppressing Nrip2\n                    <jats:sup>+<\/jats:sup>\n                    SMCs, leading to abnormal mitochondrial metabolism and VSMC phenotypic transitions. Thus, targeting leptin to boost Nrip2\n                    <jats:sup>+<\/jats:sup>\n                    VSMC metabolic activity is a promising strategy for TAD prevention and treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202502027","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T03:45:49Z","timestamp":1752723949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Leptin Aggravates Thoracic Aortic Dissection Through Impairment of Energy Metabolism in Nrip2\n                    <sup>+<\/sup>\n                    Smooth Muscle Cells"],"prefix":"10.1002","volume":"12","author":[{"given":"Ling","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Fujian Medical University Union Hospital  Fuzhou 350100 China"},{"name":"Key Laboratory of Cardio\u2010Thoracic Surgery (Fujian Medical University) Fujian Province University  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