{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:19:14Z","timestamp":1790432354682,"version":"4.1.0"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Vascular smooth muscle cells (VSMCs) undergo phenotypic changes during the development of aortic aneurysm and dissection (AAD). Metabolism shifts from oxidative phosphorylation to glycolysis. Recent studies suggest that epigenetics plays a crucial role in AAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The epigenetic regulation of histone lactylation was analyzed in the aorta of patients with aortic aneurysm and in a murine model of AAD. Histone lactylation was also studied in VSMCs treated with angiotensin II. The epigenetic pathway involving H4K16 lactylation (H4K16la) was explored in vitro and in vivo. To examine the role of H4K16la in AAD formation, mice lacking Pdk1 or Kat7 in VSMCs were created. Mice were treated with pharmacological inhibitors of Pdk1 or Kat7. The levels of blood lactate, aortic lactate, and aortic H4K16la were compared between patients with aortic aneurysm and controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Histone lactylation (H4K16la) was increased in the aortic tissues of patients with AAD and mice. Enhanced histone lactylation was linked to increased pyruvate dehydrogenase kinase 1 (PDK1) transcription, which accelerated lactate production in VSMCs. A positive feedback loop was identified involving H4K16la, PDK1, and lactate; this pathway alters the metabolism and phenotype of VSMCs. KAT7 (lysine acetyltransferase 7) was found to be a histone lactyltransferase for histone lactylation in VSMCs. Genetic or pharmacological inhibition of PDK1 or KAT7 decreased AAD injury by disrupting the H4K16la\/PDK1\/lactate pathway. Patients with AAD have elevated lactate in blood and aortic tissues and elevated H4K16la in aortic tissues compared with control patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Histone lactylation changes the metabolism and phenotype of VSMC in AAD. Inhibition of PDK1 or KAT7 may be a novel approach to treat or prevent AAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.072576","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T10:00:37Z","timestamp":1767607237000},"page":"189-209","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Histone Lactylation\u2013Mediated Metabolic Remodeling in Vascular Smooth Muscle Cells Aggravates Aortic Aneurysm and Dissection by Promoting Lactate Accumulation"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-9212","authenticated-orcid":true,"given":"Liwei","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., B.Z., A.S., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., W.L., L.P., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, China (L.L., J.Z., Z.D., Y.C., X.W., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., B.Z., A.S., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9786-3886","authenticated-orcid":true,"given":"Zhen","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., W.L., L.P., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, China (L.L., J.Z., Z.D., Y.C., X.W., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., B.Z., A.S., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3372-1352","authenticated-orcid":true,"given":"Yikai","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., B.Z., A.S., A.S., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Zou","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center (X.Z.), Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery (H.L., J.G.), Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery (H.L., J.G.), Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-0813","authenticated-orcid":true,"given":"Xinyu","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., W.L., L.P., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, China (L.L., J.Z., Z.D., Y.C., X.W., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"Institutes of 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Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., W.L., L.P., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., W.L., L.P., X.S., B.Z., A.S., A.S., J.G.)."},{"name":"State Key Laboratory of Cardiology (L.L., J.Z., Z.D., Y.C., X.W., X.J., Z.P., W.H., Y.H., X.S., B.Z., A.S., A.S., J.G.)"},{"name":"Key Laboratory of Viral Heart Diseases, National Health Commission, China (L.L., J.Z., Z.D., Y.C., X.W., W.H., Y.H., X.S., B.Z., A.S., A.S., 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J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Deaths: final data for 2018.","volume":"69","author":"Murphy SL","year":"2021","unstructured":"Murphy SL, Xu J, Kochanek KD, Arias E, Tejada-Vera B. 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