{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:15:41Z","timestamp":1792793741917,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vein graft restenosis is a leading cause of long-term failure after coronary artery bypass grafting (CABG), driven by maladaptive vascular smooth muscle cell (VSMC) responses to arterialization-induced inflammation. The key molecular mediators of this pathological remodeling, however, remain incompletely defined. Here, we integrated multi-omics analyses of human and canine vein graft specimens with in vitro functional assays to identify tenascin-C (TNC)\u2014a matricellular extracellular matrix protein\u2014as a critical regulator of VSMC dysfunction. TNC was specifically enriched in a synthetic, pro-inflammatory VSMC subpopulation. Pro-inflammatory stimuli potently induced TNC expression, which was functionally linked to VSMC phenotypic modulation, hyperproliferation, and enhanced migration. Mechanistically, TNC acts upstream of NF-\u03baB signaling; siRNA-mediated TNC knockdown significantly reduced nuclear p65 protein levels and attenuated inflammatory responses. Our integrated computational and experimental data suggest that TNC, NF-\u03baB, and TNF-\u03b1 function within a sequential pro-inflammatory signaling cascade that sustains vascular inflammation and promotes neointimal hyperplasia. These findings reposition TNC from a passive structural component to an active driver of vascular pathology and highlight the TNC\u2013NF-\u03baB axis as a candidate target for therapeutic intervention to improve vein graft patency.<\/jats:p>","DOI":"10.3390\/ijms27125516","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tenascin-C Drives Inflammatory VSMC Phenotypic Switching Through NF-\u03baB Signaling in Saphenous Vein Graft Restenosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Lipeng","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enyi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.jacc.2004.08.064","article-title":"Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: Results from a Department of Veterans Affairs Cooperative Study","volume":"44","author":"Goldman","year":"2004","journal-title":"J. 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