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Immune cells are recognized drivers of aneurysm pathogenesis. Clonal hematopoiesis is an age-related expansion of somatically mutated hematopoietic stem cells that reshapes immune function and contributes to diverse age-associated diseases. However, its contribution to aneurysm pathogenesis remains unclear. In this study, targeted ultradeep sequencing of patient specimens revealed a high prevalence of clonal hematopoiesis\u2013associated mutations that correlated with faster aneurysm expansion. Thus, we modeled clonal hematopoiesis by competitively transplanting ten-eleven translocation 2\u2013deficient (\n                    <jats:italic>Tet2<\/jats:italic>\n                    -deficient) bone marrow into apoliprotein E\u2013KO (\n                    <jats:italic>Apoe<\/jats:italic>\n                    -KO) mice and induced aneurysms with angiotensin II. Mice with Tet2 clonal hematopoiesis developed significantly greater aortic dilation than did controls. Interestingly,\n                    <jats:italic>Tet2<\/jats:italic>\n                    -deficient macrophages adopted an acid phosphatase 5, tartrate resistant (ACP5\n                    <jats:sup>+<\/jats:sup>\n                    ), osteoclast-like state and produced more matrix metalloproteinase 9 (MMP9). Both genetic and pharmacological inhibition of osteoclast-like differentiation suppressed the Tet2-mediated aneurysmal growth in vivo. Thus, Tet2-driven clonal hematopoiesis accelerated aortic aneurysm progression through MMP9-producing, osteoclast-like macrophages and therefore represents a tractable therapeutic axis.\n                  <\/jats:p>","DOI":"10.1172\/jci198708","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T17:00:22Z","timestamp":1772038822000},"source":"Crossref","is-referenced-by-count":2,"title":["Tet2-driven clonal hematopoiesis drives aortic aneurysm via macrophage-to-osteoclast\u2013like differentiation"],"prefix":"10.1172","volume":"136","author":[{"given":"Jun","family":"Yonekawa","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimitsu","family":"Yura","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmiao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-1451","authenticated-orcid":true,"given":"Katsuhiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuta","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan."},{"name":"Department of Vascular Surgery, Aichi Medical University, Nagakute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Kizuki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiri","family":"Miura-Yura","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Horitani","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Kansai Medical University, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Duk","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Renal Medicine, Hyogo Medical University, Hyogo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuo","family":"Emoto","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Banno","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikito","family":"Takefuji","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-2276","authenticated-orcid":true,"given":"Kenneth","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Robert M. 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