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We here show the involvement of perivascular inflammation in aortic dilatation of Marfan syndrome (MFS). In the aorta of patients with MFS and\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice, macrophages markedly accumulated in periaortic tissues with increased inflammatory cytokine expression. Metabolic inflammatory stress induced by a high-fat diet (HFD) enhanced vascular inflammation predominantly in periaortic tissues and accelerated aortic dilatation in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice, both of which were inhibited by low-dose pitavastatin. HFD feeding also intensifies structural disorganization of the tunica media in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice, including elastic fiber fragmentation, fibrosis, and proteoglycan accumulation, along with increased activation of TGF-\u03b2 downstream targets. Pitavastatin treatment mitigated these alterations. For noninvasive assessment of perivascular adipose tissues (PVAT) inflammation in a clinical setting, we developed an automated analysis program for CT images using machine learning techniques to calculate the perivascular fat attenuation index of the ascending aorta (AA-FAI), correlating with periaortic fat inflammation. The AA-FAI was significantly higher in patients with MFS compared with patients without hereditary connective tissue disorders. These results suggest that perivascular inflammation contributes to aneurysm formation in MFS and might be a target for preventing and treating vascular events in MFS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184329","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T16:00:27Z","timestamp":1756396827000},"source":"Crossref","is-referenced-by-count":10,"title":["Perivascular inflammation in the progression of aortic aneurysms in Marfan syndrome"],"prefix":"10.1172","volume":"10","author":[{"given":"Hiroyuki","family":"Sowa","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6615-6196","authenticated-orcid":true,"given":"Hiroki","family":"Yagi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine,"},{"name":"Marfan 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