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However, molecular mechanisms underlying TAA pathogenesis remain to be fully elucidated. The aorta is naturally surrounded by perivascular adipose tissue (PVAT), which produces and releases adipokines and other factors in a paracrine manner that are pivotal for vascular physiology and pathophysiology. Under healthy conditions, thoracic PVAT resembles brown adipose tissue (BAT) and maintains vascular homeostasis. In response to pathogenic stimuli, PVAT can undergo whitening and become dysfunctional, contributing to the development of vascular diseases. However, a causal relationship between PVAT dysfunction and TAA pathogenesis, as well as the underlying mechanisms, remain unknown. This study investigated the roles of PPARg (a key determinant of adipogenesis) and PRDM16 (a key determinant of brown adipocyte development) in PVAT on TAA development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PVAT samples from TAA patients were collected and evaluated. Mice lacking PVAT and those with dysfunctional PVAT were generated by crossbreeding\n                      <jats:italic>Ucp1<\/jats:italic>\n                      promoter-driven Cre mice with\n                      <jats:italic>Pparg<\/jats:italic>\n                      floxed mice (brown adipocyte-specific\n                      <jats:italic>Pparg<\/jats:italic>\n                      knockout,\n                      <jats:italic>Pparg<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      ) and\n                      <jats:italic>Prdm16<\/jats:italic>\n                      floxed mice (brown adipocyte-specific\n                      <jats:italic>Prdm16<\/jats:italic>\n                      knockout,\n                      <jats:italic>Prdm16<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      ), respectively. TAA formation was induced by perivascular application of porcine pancreatic elastase (PPE) and evaluated through histological staining. Luciferase reporter assays and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) were used to determine PRDM16 target genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that PVAT near TAA lesions in patients exhibited reduced expression of browning markers and increased expression of whitening markers.\n                      <jats:italic>Pparg<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      mice showed impaired PVAT development, while\n                      <jats:italic>Prdm16<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      mice displayed a loss of browning in PVAT. Both\n                      <jats:italic>Pparg<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      and\n                      <jats:italic>Prdm16<\/jats:italic>\n                      <jats:sup>BAKO<\/jats:sup>\n                      mice exhibited aggravated TAA formation. We identified decorin, a small proteoglycan of the extracellular matrix, as a transcriptional repressive target gene of PRDM16. The expression of decorin was increased in dysfunctional PVAT and the plasma of TAA patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The development and maintenance of brown-like characteristics in PVAT are necessary to protect against TAA formation. PVAT dysfunction contributes to TAA development. Our study provides a promising therapeutic strategy for preventing TAA progression by inducing PVAT browning.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-025-02765-x","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:37:00Z","timestamp":1747813020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Perivascular adipose tissue dysfunction contributes to thoracic aortic aneurysm development"],"prefix":"10.1186","volume":"24","author":[{"given":"Zhenguo","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiubin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Sheng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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Human aortic tissues were obtained from the Department of Cardiac Surgery at the University of Michigan with Institutional Review Board approval (HUM00117884, HUM00077616) with patients\u2019 consent, and in accordance with the Declaration of Helsinki. The specimens in this study were de-identified (i.e., all identifiers and links have been destroyed).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"223"}}