{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:21:50Z","timestamp":1793164910801,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The dysregulated immune system, which drives chronic vascular inflammation and remodeling, plays a critical role in the pathogenesis of abdominal aortic aneurysm (AAA). CCR4 (C\u2010C chemokine receptor 4), which is predominantly expressed on T cells and mediates their responses, has been shown to protect against inflammatory diseases including atherosclerosis. However, its role in AAA remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      By analyzing hypercholesterolemic CCR4\u2010deficient (\n                      <jats:italic toggle=\"no\">Ccr4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice on an apolipoprotein E\u2010deficient (\n                      <jats:italic toggle=\"no\">Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) background, we investigated the role of CCR4 in the development of angiotensin II\u2010induced AAA, with a particular focus on T\u2010cell\u2010mediated immune responses, by performing histological analysis, flow cytometry, biochemical assays, and single\u2010cell RNA sequencing analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Genetic deletion of CCR4 on an\n                      <jats:italic toggle=\"no\">Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      background dramatically reduced the incidence and severity of angiotensin II\u2010induced AAA without affecting mortality due to rupture, along with attenuated inflammatory cell recruitment and preserved elastic lamellae in the aorta. This protective effect was associated with a shift in the T helper cell balance toward T helper type 1 predominance, characterized by promoted IFN\u2010\u03b3 (interferon\u2010gamma) production and suppressed B\u2010cell\u2010mediated IgE production. Single\u2010cell RNA sequencing analysis of abdominal aortic tissues revealed lower proportions of myofibroblasts and modulated smooth muscle cells highly expressing genes associated with extracellular matrix remodeling in angiotensin II\u2010infused\n                      <jats:italic toggle=\"no\">Ccr4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:italic toggle=\"no\">Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, potentially driven by downregulated TGF\u2010\u03b2 (transforming growth factor\u2010beta) signaling due to increased T helper type 1 cell\u2010derived IFN\u2010\u03b3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">CCR4 may serve as a potential therapeutic target for AAA.<\/jats:p>\n         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