{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:05:34Z","timestamp":1792065934864,"version":"4.4.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The development of thoracic aortic dissection (TAD) is closely related to extracellular matrix degradation and vascular smooth muscle cell (VSMC) transformation from contractile to synthetic type. LGMN (legumain) degrades extracellular matrix components directly or by activating downstream signals. The role of LGMN in VSMC differentiation and the occurrence of TAD remains elusive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Microarray datasets concerning vascular dissection or aneurysm were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes. Four-week-old male\n              <jats:italic>Lgmn<\/jats:italic>\n              knockout mice (Lgmn\n              <jats:sup>\u2013\/\u2013<\/jats:sup>\n              ), macrophage-specific\n              <jats:italic>Lgmn<\/jats:italic>\n              knockout mice (Lgmn\n              <jats:sup>F\/F<\/jats:sup>\n              ;LysM\n              <jats:sup>Cre<\/jats:sup>\n              ), and RR-11a\u2013treated C57BL\/6 mice were given BAPN (\u03b2-aminopropionitrile monofumarate; 1 g\/kg\/d) in drinking water for 4 weeks for TAD modeling. RNA sequencing analysis was performed to recapitulate transcriptome profile changes. Cell interaction was examined in macrophage and VSMC coculture system. The reciprocity of macrophage-derived LGMN with integrin \u03b1v\u03b23 in VSMCs was tested by coimmunoprecipitation assay and colocalization analyses.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Microarray datasets from the Gene Expression Omnibus database indicated upregulated LGMN in aorta from patients with TAD and mice with angiotensin II\u2013induced AAA. Elevated LGMN was evidenced in aorta and sera from patients with TAD and mice with BAPN-induced TAD. BAPN-induced TAD progression was significantly ameliorated in Lgmn-deficient or inhibited mice. Macrophage-specific deletion of\n              <jats:italic>Lgmn<\/jats:italic>\n              alleviated BAPN-induced extracellular matrix degradation. Unbiased profiler polymerase chain reaction array and Gene Ontology analysis displayed that\n              <jats:italic>LGMN<\/jats:italic>\n              regulated VSMC phenotype transformation. Macrophage-specific deletion of\n              <jats:italic>Lgmn<\/jats:italic>\n              ameliorated VSMC phenotypic switch in BAPN-treated mice. Macrophage-derived LGMN inhibited VSMC differentiation in vitro as assessed by macrophages and the VSMC coculture system. Macrophage-derived LGMN bound to integrin \u03b1v\u03b23 in VSMCs and blocked integrin \u03b1v\u03b23, thereby attenuating Rho GTPase activation, downregulating VSMC differentiation markers and eventually exacerbating TAD development. ROCK (Rho kinase) inhibitor Y-27632 reversed the protective role of LGMN depletion in vascular dissection.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>LGMN signaling may be a novel target for the prevention and treatment of TAD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.121.056640","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T23:51:12Z","timestamp":1643673072000},"page":"659-674","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":172,"title":["Legumain Is an Endogenous Modulator of Integrin \u03b1v\u03b23 Triggering Vascular Degeneration, Dissection, and Rupture"],"prefix":"10.1161","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1995-2373","authenticated-orcid":true,"given":"Lihong","family":"Pan","sequence":"first","affiliation":[{"name":"Institutes 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