{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:12:02Z","timestamp":1789589522478,"version":"build-2803163510"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Foundation of China","award":["82170499,81921001,31930056,82170490,82100436,81800259"],"award-info":[{"award-number":["82170499,81921001,31930056,82170490,82100436,81800259"]}]},{"name":"the Special Fund for Talents from Peking University","award":["71015Y2387,68263Y1241"],"award-info":[{"award-number":["71015Y2387,68263Y1241"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,16]]},"abstract":"<jats:p>\n                    The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell\u2013mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages mainly located in the intima in the aortic roots and ascending aortas of\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, further validated in MFS patients. Specific elimination of CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    cells by diphtheria toxin in\n                    <jats:italic>Cx3cr1<\/jats:italic>\n                    -CreER\n                    <jats:sup>T2<\/jats:sup>\n                    iDTR\n                    <jats:sup>F\/+<\/jats:sup>\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice efficiently ameliorated TAA progression. Administering the monoclonal antibodies to respectively neutralize TNF-\u03b1 and IGF1 produced by CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    cells from MFS patients greatly suppressed the cocultured MFS patient\u2013specific induced pluripotent stem cell\u2013derived VSMC inflammation. BM transplantation and parabiosis revealed that CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages are mainly originated from BM-derived monocytes. Targeting TNF-\u03b1 and IGF1 in CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages via shRNA lentivirus transduction in BM cells efficiently suppressed TAA development in BM-transplanted\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Application of the CCR2 antagonist RS504393 to inhibit monocyte infiltration markedly reduced the accumulation of CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages and subsequently alleviated TAA progression in\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1041G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice. In summary, CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages mainly located in aortic intima mediate TAA formation by paracrinally causing VSMC inflammation, and targeting them offers a potential antiinflammatory therapeutic strategy for MFS-related TAA.\n                  <\/jats:p>","DOI":"10.1172\/jci178198","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:44Z","timestamp":1736949644000},"source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice"],"prefix":"10.1172","volume":"135","author":[{"given":"Jiaqi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Beijing Anzhen Hospital of Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Engineering Research Center of Vascular Prostheses, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenting","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking 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