{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:05:49Z","timestamp":1784649949300,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Coronary artery bypass grafting (CABG) is the standard revascularization procedure, and the left internal mammary artery (LIMA) is the most widely used conduit owing to its long-term patency and favorable impact on survival. Although fibrosis and calcification are comparatively infrequent in internal mammary artery (IMA) grafts, progressive remodeling may still compromise patency. Tumor necrosis factor-\u03b1 (TNF-\u03b1) is a pro-inflammatory cytokine implicated in vascular remodeling and calcification, whereas L-arginine, a precursor of nitric oxide, may exert vasoprotective effects. Aim: To investigate the effects of ex vivo TNF-\u03b1 and combined TNF-\u03b1 plus L-arginine treatment on the morphology, calcification, elemental composition, and biomechanical properties of human LIMA grafts. Patients and Methods: LIMA graft segments from 18 male CABG patients were allocated to one control group (G0) and two ex vivo treatment groups. Grafts were assessed using hematoxylin and eosin and Masson\u2019s Trichrome staining under brightfield microscopy, using Alizarin Red S fluorescence staining to measure calcification, and by scanning electron microscopy with energy-dispersive spectroscopy (SEM\/EDS) to assess ultrastructure and elemental composition. Scanning acoustic microscopy (SAM) was used to derive acoustic impedance as a label-free index of tissue stiffness. Results: TNF-\u03b1 treatment was associated with increased acoustic impedance, consistent with graft stiffening, together with greater calcification signatures, whereas combined TNF-\u03b1 and L-arginine treatment shifted impedance toward control-like values and showed more organized tissue architectures with reduced calcification. Conclusions: In this preliminary ex vivo model, L-arginine attenuated TNF-\u03b1-associated remodeling and stiffening of LIMA grafts, suggesting a potential role in supporting graft durability; larger, statistically powered studies with molecular validation are required to confirm these findings.<\/jats:p>","DOI":"10.3390\/jcm15145716","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:17:52Z","timestamp":1784647072000},"page":"5716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of TNF-\u03b1 and L-Arginine Ex Vivo Treatment on Left Internal Mammary Artery (LIMA) Grafts"],"prefix":"10.3390","volume":"15","author":[{"given":"Beste","family":"Dipcin","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"},{"name":"Acibadem University (ACU) Biomaterials A and R Center, Acibadem Mehmet Ali Aydinlar University (ACU), Atasehir, Istanbul 34752, Turkey"},{"name":"Department of Biomedical Engineering, Graduate School of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ataei","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Graduate School of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Turan","family":"Keskintas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"},{"name":"Experimental Medicine Research and Application Center, Validebag Research Park, University of Health Sciences, Uskudar, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokcen","family":"Ozgun","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-9479","authenticated-orcid":false,"given":"Sevde","family":"Altuntas","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research and Application Center, Validebag Research Park, University of Health Sciences, Uskudar, Istanbul 34668, Turkey"},{"name":"Department of Tissue Engineering, University of Health Sciences, Uskudar, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"Onal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Biruni University, Istanbul 34015, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutfi \u00c7a\u011fatay","family":"Onar","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Republic of Turkey Ministry of Health, Dr. Ismail Fehmi Cumalioglu City Hospital, Tekirdag 59020, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem Melis","family":"Oztas","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Liv Hospital Vadistanbul, Istanbul 34015, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-0501","authenticated-orcid":false,"given":"Bukem","family":"Tanoren","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Faculty of Engineering and Natural Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Ugurlucan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Liv Hospital Vadistanbul, Istanbul 34015, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ansari, S. 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