{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:01:55Z","timestamp":1788184915796,"version":"build-2803163510"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)\/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Transcriptome data from human and mouse ADs were used to perform differentially expressed gene\u2013based protein-protein interaction network analyses.\n              <jats:italic>Tyrobp<\/jats:italic>\n              knockout (Tyrobp\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ), myeloid cell\u2013specific\n              <jats:italic>Tyrobp<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (Tyrobp\n              <jats:sup>fl\/fl<\/jats:sup>\n              Lyz2\n              <jats:sup>cre<\/jats:sup>\n              ), and\n              <jats:italic>Trem2<\/jats:italic>\n              knockout (Trem2\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) mice were given \u03b2-aminopropionitrile monofumarate in drinking water to induce AD. To dissect the role of macrophages in\n              <jats:italic>Tyrobp<\/jats:italic>\n              deficiency\u2013mediated AD progression, macrophages were depleted using clodronate liposomes. Bulk and single-cell RNA sequencing, immunofluorescence staining, and quantitative real-time polymerase chain reaction were performed to assess inflammation and the underlying mechanisms of Tyrobp in AD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Network analysis identified\n              <jats:italic>Tyrobp<\/jats:italic>\n              as a hub gene of AD, with elevated levels observed in both human and mouse ADs. Global deletion and myeloid cell\u2013specific deficiency of\n              <jats:italic>Tyrobp<\/jats:italic>\n              in mice significantly increased AD incidence and exacerbated extracellular matrix degradation and macrophage infiltration within the aortic wall. Macrophage depletion mitigated the adverse effects of\n              <jats:italic>Tyrobp<\/jats:italic>\n              deficiency on AD progression. Additionally,\n              <jats:italic>Tyrobp<\/jats:italic>\n              deficiency enhanced TLR (Toll-like receptor)-4 signaling and macrophage activation, which were abrogated by TLR4 inhibitors. Furthermore, deletion of the Tyrobp-associated receptor\n              <jats:italic>Trem2<\/jats:italic>\n              significantly aggravated mouse AD development, whereas Trem2 agonist treatment conferred protection against AD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our findings suggest a novel role for the Trem2\/Tyrobp axis in AD development in mice. Enhancement of Trem2\/Tyrobp signaling may represent a promising strategy for the prevention and treatment of AD. Future studies to clarify the role of Trem2\/Tyrobp in human AD are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321429","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T10:00:39Z","timestamp":1730973639000},"page":"119-135","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Trem2\/Tyrobp Signaling Protects Against Aortic Dissection and Rupture by Inhibiting Macrophage Activation in Mice"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6600-1554","authenticated-orcid":true,"given":"Zenghui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (Z.Z., M.W., L.Y., W.Z., X.L., Z.C., C.L., C.H., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Z.L., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Department of Cardiology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China (Z.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-2763","authenticated-orcid":true,"given":"Maoxiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (Z.Z., M.W., L.Y., W.Z., X.L., Z.C., C.L., C.H., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Z.L., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3585-1478","authenticated-orcid":true,"given":"Lei","family":"Yao","sequence":"additional","affiliation":[{"name":"Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (Z.Z., M.W., L.Y., W.Z., X.L., Z.C., C.L., C.H., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Z.L., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9921-9407","authenticated-orcid":true,"given":"Weibin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8954-2364","authenticated-orcid":true,"given":"Zhaoqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (Z.Z., M.W., L.Y., W.Z., X.L., Z.C., C.L., C.H., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Z.L., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology (Z.Z., M.W., W.Z., X.L., Z.C., C.L., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (Z.Z., M.W., L.Y., W.Z., X.L., Z.C., C.L., C.H., S.C., Z.H., Y.H., J.H., T.C., J.W., W.Y., Z.L., Y.C.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China."},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology (Z.Z., M.W., W.Z., 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