{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:13:26Z","timestamp":1789665206165,"version":"4.0.1"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet\u2013induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a \u03b2-aminopropionitrile diet, Marfan mice with\n              <jats:italic toggle=\"yes\">fibrillin-1<\/jats:italic>\n              haploinsufficiency (\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1041G\/+<\/jats:italic>\n              <\/jats:sup>\n              ), and\n              <jats:italic toggle=\"yes\">ApoE<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in \u03b2-aminopropionitrile\u2013treated mice,\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1041G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice, and Ang II\u2013infused\n              <jats:italic toggle=\"yes\">ApoE<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that Fc\u03b3R (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated Fc\u03b3R-mediated ERK1\/2 (extracellular signal-regulated kinase 1\/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or Fc\u03b3R deficiency.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid\u2013lowering drug may represent a promising therapeutic approach for TAAD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318788","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T05:02:00Z","timestamp":1682571720000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice"],"prefix":"10.1161","volume":"43","author":[{"given":"Liu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, China (L.Y., H.W., R.D., Z.L., X.Z., Z.G., Z.C., Y.S., F.Y., Y.F., W.K.)."},{"name":"Wuxi School of Medicine, Jiangnan University, Wuxi, China (L.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, China (L.Y., H.W., R.D., Z.L., X.Z., Z.G., Z.C., Y.S., F.Y., Y.F., W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Beijing Aortic Disease Center, Beijing Anzhen Hospital, Capital Medical University, China (C.L., J.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China (Y.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongbo","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, China (L.Y., H.W., R.D., Z.L., X.Z., Z.G., Z.C., Y.S., F.Y., Y.F., W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, China (L.Y., H.W., R.D., Z.L., X.Z., Z.G., Z.C., Y.S., F.Y., Y.F., W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, 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