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However, key ECM components regulating vascular integrity and remodelling remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Transcriptome profiling and studies in human AAA and in aneurysms from two models susceptible to angiotensin II (Ang II)\u2010induced AAA\u2014apolipoprotein E knockout mice (ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) and transgenic mice overexpressing the nuclear receptor NOR\u20101 in the vasculature (TgNOR\u20101\n                      <jats:sup>VSMC<\/jats:sup>\n                      )\u2014were carried out. Thrombospondin (\n                      <jats:italic>THBS4<\/jats:italic>\n                      , TSP4) was knocked down\n                      <jats:italic>in vivo<\/jats:italic>\n                      by lentiviral RNA interference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      Transcriptome profiling highlighted the relevance of the ECM\u2010mediated pathway and the upregulation of\n                      <jats:italic>THBS4<\/jats:italic>\n                      in human AAA. In a large cohort of patients and donors and in Ang II\u2010infused ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and TgNOR\u20101\n                      <jats:sup>VSMC<\/jats:sup>\n                      mice, we confirmed the significant increase of aortic\n                      <jats:italic>THBS4<\/jats:italic>\n                      mRNA and TSP4 protein levels in AAA and found that\n                      <jats:italic>THBS4<\/jats:italic>\n                      was early upregulated in pre\u2010aneurysmal lesions.\n                      <jats:italic>THBS4<\/jats:italic>\n                      was mainly detected in the adventitia of mouse aorta and in cell cultures from fibroblasts or IFN\u03b3\u2010stimulated macrophages. Accordingly, in AAA, TSP4 immunostaining was predominant in adventitial fibroblasts and macrophages.\n                      <jats:italic>Thbs4<\/jats:italic>\n                      blockade shifted macrophages and fibroblasts towards a more pro\u2010inflammatory phenotype, whereas, in Ang II\u2010challenged ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, aortic\n                      <jats:italic>Thbs4<\/jats:italic>\n                      knockdown by lentiviral transduction accelerated disease progression, increasing aortic diameter and aggravating both vascular inflammation and remodelling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>We uncover the early and sustained induction of TSP4 in AAA and its protective role in limiting vascular inflammation and destructive remodelling. Modulation of TSP4\u2010dependent pathways may represent a novel avenue to improve vascular stability in AAA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70402","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:32:02Z","timestamp":1773297122000},"page":"3321-3339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thrombospondin\u20104 is upregulated in abdominal aortic aneurysm: A vasoprotective response with potential therapeutic relevance"],"prefix":"10.1111","volume":"183","author":[{"given":"Laia","family":"Blanco\u2010Casoliva","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas de Barcelona\u2010Consejo Superior de Investigaciones Cient\u00edficas (IIBB\u2010CSIC)  Barcelona Spain"},{"name":"Institut de Recerca Sant Pau (IR SANT PAU)  Barcelona 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