{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:41:26Z","timestamp":1790401286387,"version":"4.1.0"},"reference-count":48,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p> In weeks to months following implantation, neointimal hyperplasia (NIH) in vein grafts (VGs) transitions from a cellularized to a decellularized phenotype. The inhibition of early cellular proliferation failed to improve long-term VG patency. We have previously demonstrated that transforming growth factor-\u03b2<jats:sub>1<\/jats:sub> (TGF-\u03b2<jats:sub>1<\/jats:sub>)\/connective tissue growth factor (CTGF) pathways mediate a conversion of fibroblasts to myofibroblasts in the early VG (&lt;2 wk). We hypothesize that these similar pathways drive fibrosis observed in the late VG lesion. Within rabbit VGs, real-time RT-PCR, Western blot analysis, ELISA, and immunohistochemistry were used to examine TGF-\u03b2\/CTGF pathways in late (1\u20136 mo) NIH. All VGs exhibited a steady NIH growth ( P = 0.006) with significant reduction in cellularity ( P = 0.01) over time. Substantial TGF-\u03b2 profibrotic activities, as evidenced by enhanced TGF-\u03b2<jats:sub>1<\/jats:sub> activation, TGF-\u03b2 receptor types I (activin receptor-like kinase 5)-to-II receptor ratio, SMAD2\/3 phosphorylation, and CTGF production, persisted throughout the observation period. An increased matrix synthesis was accompanied by a temporal reduction of matrix metalloproteinase-2 ( P = 0.001) and -9 ( P &lt; 0.001) activity. VG NIH is characterized by a conversion from a proproliferative to a profibrotic morphology. An enhanced signaling via TGF-\u03b2\/CTGF coupled with reduced matrix metalloproteinase activities promotes progressive fibrotic NIH expansion. The modulation of late TGF-\u03b2\/CTGF signaling may offer a novel therapeutic strategy to improve the long-term VG durability. <\/jats:p>","DOI":"10.1152\/ajpheart.00268.2009","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T21:48:49Z","timestamp":1247867329000},"page":"H1200-H1207","source":"Crossref","is-referenced-by-count":53,"title":["Established neointimal hyperplasia in vein grafts expands via TGF-\u03b2-mediated progressive fibrosis"],"prefix":"10.1152","volume":"297","author":[{"given":"Zhihua","family":"Jiang","sequence":"first","affiliation":[{"name":"University of Florida College of Medicine and the Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Tao","sequence":"additional","affiliation":[{"name":"Harvard Medical School Brigham and Women's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri A.","family":"Omalley","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine and the Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danlu","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine and the Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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