{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:21:47Z","timestamp":1793164907834,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Abdominal aortic aneurysms and dissections (AAA\/AD) are vascular disorders with high mortality due to aortic ruptures. Critical pathomechanisms involve immune cell infiltration and degradation of the vascular extracellular matrix (ECM). Hyaluronan (HA), a major constituent of the ECM synthesized by three HA synthase isoenzymes (HAS1-3), plays a role in both processes. Specifically, HAS3 is crucially involved in inflammatory conditions. Here, we aimed to elucidate the role of HAS3-derived HA in AAA\/AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice double-deficient for\n                      <jats:italic>apolipoprotein E<\/jats:italic>\n                      and\n                      <jats:italic>Has3<\/jats:italic>\n                      (\n                      <jats:italic>Apoe\/Has3<\/jats:italic>\n                      -DKO) and littermate controls (\n                      <jats:italic>Apoe<\/jats:italic>\n                      -KO) were studied in a model of angiotensin II (AngII)-induced AAA\/AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Has3<\/jats:italic>\n                      deficiency improved survival in\n                      <jats:italic>Apoe\/Has3<\/jats:italic>\n                      -DKO mice\n                      <jats:italic>via<\/jats:italic>\n                      reducing aortic ruptures. This was associated with decreased monocyte infiltration into the vessel wall. Aortic RNA-Seq analysis indicated disturbed immune cell adhesion and diapedesis. Transfer of\n                      <jats:italic>Apoe-<\/jats:italic>\n                      deficient bone marrow into\n                      <jats:italic>Apoe\/Has3<\/jats:italic>\n                      -DKO mice largely normalized the\n                      <jats:italic>Apoe\/Has3<\/jats:italic>\n                      -DKO phenotype. While gene expression in endothelial cells (ECs) was not affected, AngII-induced upregulation of proinflammatory cytokines, adhesion receptors and the HA receptor CD44 was attenuated in\n                      <jats:italic>Apoe\/Has3-<\/jats:italic>\n                      DKO monocytes. This reduced CD44 cell surface expression in\n                      <jats:italic>Apoe\/Has3-<\/jats:italic>\n                      double-deficient monocytes, ultimately inhibiting their\n                      <jats:italic>in vitro<\/jats:italic>\n                      transmigration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results show that HAS3 plays a key role in AAA\/AD formation and suggest the HAS3\/CD44 axis as promising therapeutic target to reduce monocyte recruitment and aortic rupture.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1680246","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T13:03:56Z","timestamp":1762434236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hyaluronan synthase 3 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