{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:22:53Z","timestamp":1789093373489,"version":"build-2803163510"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Thoracic aortic dissection (TAD) is a life-threatening aortic disease without effective medical treatment. Disruption of vascular smooth muscle cell (VSMC) homeostasis plays a vital role in triggering TAD. ELA (ELABELA) is a novel endogenous ligand for APJ (angiotensin receptor AT1\u2013related receptor protein). However, the effects of ELA on TAD formation and development remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Four-week-old C57BL\/6J male mice were treated with \u03b2-aminopropionitrile monofumarate or \u03b2-aminopropionitrile monofumarate combined with Ang II (angiotensin II) to induce TAD models, and the aortic rupture occurred mainly in the descending thoracic region. ELA or saline was infused via osmotic minipumps into mice for 4 weeks. Transcriptomic studies and VSMC-derived conditioned medium were used to investigate the downstream molecular mechanisms of ELA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>ELA infusion mitigated TAD development and prevented aortic media degradation in mice, which was reversed by APJ antagonist ML221. Exogenous ELA prevented the disruption of VSMC homeostasis under PDGF (platelet-derived growth factor) stimulation in VSMCs. Based on transcriptomic studies, we showed that ELA significantly inhibits NLRP3 (NLR family pyrin domain-containing 3)\/IL (interleukin)-1\u03b2 pathway activation and modulates NET (neutrophil extracellular trap) formation in vivo and in vitro. In human neutrophils, ELA significantly inhibited NETs\u2019 formation, which is prevented by reactive oxidative species supplementation. Using VSMC-derived conditioned medium, we showed that NLRP3\/IL-1\u03b2\u2013related NETs\u2019 formation connects cellular signaling from VSMCs to neutrophils, leading to disruption of VSMC homeostasis. Notably, ELA was downregulated in both plasma and aortic tissues of human TAD, and lower plasma ELA levels were associated with an increased risk of TAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We provide evidence that ELA prevents TAD progression and aortic medial degeneration, primarily by maintaining VSMC homeostasis, which may be linked to the inhibition of NETosis in neutrophils and NLRP3\/IL-1\u03b2\u2013related cellular signaling between VSMCs and neutrophils. ELA shows promise as a target for pharmacological therapy and diagnostic TAD management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.324169","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:00:52Z","timestamp":1772704852000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["ELABELA Protects Against Thoracic Aortic Dissection by Maintaining Vascular Smooth Muscle Cells Homeostasis and Regulating NETosis"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-7802","authenticated-orcid":true,"given":"Fen","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology (F.Z., M.H., H.S., Y.Z., A.J., W.H., A.C., J.W., X.X.), Nanjing Medical University, China."},{"name":"The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine (F.Z., M.S., J.W.), Nanjing Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5844-7753","authenticated-orcid":true,"given":"Zhi","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The Second Affiliated Hospital of Nanjing Medical University, China (Z.G., Q.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-0085","authenticated-orcid":true,"given":"Chao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, China (C.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1021-7922","authenticated-orcid":true,"given":"Mingyu","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology (F.Z., M.H., H.S., Y.Z., A.J., W.H., A.C., J.W., X.X.), Nanjing Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0536-4096","authenticated-orcid":true,"given":"Min","family":"Sha","sequence":"additional","affiliation":[{"name":"The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine (F.Z., M.S., J.W.), Nanjing Medical University, 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