{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:37Z","timestamp":1785404197793,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2022-NR069133"],"award-info":[{"award-number":["RS-2022-NR069133"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-24536036"],"award-info":[{"award-number":["RS-2025-24536036"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2022-NR069133"],"award-info":[{"award-number":["RS-2022-NR069133"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-24536036"],"award-info":[{"award-number":["RS-2025-24536036"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare","award":["RS-2023-00302146"],"award-info":[{"award-number":["RS-2023-00302146"]}]},{"name":"Ministry of Health & Welfare","award":["RS-2023-00302153"],"award-info":[{"award-number":["RS-2023-00302153"]}]},{"award":["RS-2023-00302146"],"award-info":[{"award-number":["RS-2023-00302146"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2023-00302153"],"award-info":[{"award-number":["RS-2023-00302153"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Vascular calcification is an actively regulated process driven by vascular smooth muscle cell (VSMC) osteogenic reprogramming and promoted by oxidative stress and extracellular matrix remodeling. We investigated whether the novel histone deacetylase inhibitor YAK577 mitigates calcification by modulating an MMP14\u2013NOX2\/ROS-associated pathway in calcification medium (CM)-treated VSMCs and a vitamin D3-induced arterial calcification model in 8-week-old male C57BL\/6N mice. Calcification was assessed by Alizarin Red S\/von Kossa staining and calcium quantification; osteogenic markers (BMP2, RUNX2, MSX2) and MMPs were examined by qRT-PCR and immunoblotting; intracellular ROS was measured by DHE staining with N-acetylcysteine as an antioxidant control; and MMP14 was manipulated by siRNA knockdown or plasmid overexpression. YAK577 was non-cytotoxic at effective concentrations and reduced CM-induced calcium deposition and osteogenic marker expression. YAK577 reduced MMP14 expression and suppressed CM-induced NOX2\/p47phox activation and ROS accumulation, while GSK2795039 attenuated CM-induced DHE fluorescence. MMP14 silencing attenuated, whereas MMP14 overexpression enhanced, osteogenic signaling and increased NOX2. In vivo, YAK577 reduced vitamin D3-induced aortic calcium burden, histological calcification, and the expression of MMP14, NOX2, and osteogenic markers. These data support a working model in which YAK577 alleviates vascular calcification, at least in part, by suppressing an MMP14-associated NOX2\/p47phox\u2013ROS axis.<\/jats:p>","DOI":"10.3390\/antiox15050605","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["YAK577 Attenuates Vascular Calcification by Targeting an MMP14\u2013NOX2\/ROS Axis in VSMCs and a Vitamin D3-Induced Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3244-5840","authenticated-orcid":false,"given":"Hongyan","family":"Zhou","sequence":"first","affiliation":[{"name":"Heart Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"},{"name":"Hypertension Heart Failure Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-4828","authenticated-orcid":false,"given":"Hae Jin","family":"Kee","sequence":"additional","affiliation":[{"name":"Heart Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"},{"name":"Hypertension Heart Failure Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"},{"name":"Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Min","family":"Jeong","sequence":"additional","affiliation":[{"name":"Heart Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"},{"name":"Hypertension Heart Failure Research Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Bai","sequence":"additional","affiliation":[{"name":"Emergency Critical Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1303-1875","authenticated-orcid":false,"given":"Le","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2533-8441","authenticated-orcid":false,"given":"Seong Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"},{"name":"Department of Biomedical Sciences, Graduate School of Chonnam National University, Hwasun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2337-7826","authenticated-orcid":false,"given":"Seung Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9474-4224","authenticated-orcid":false,"given":"Thomas","family":"Kurz","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstr\u03b2e 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4162-7902","authenticated-orcid":false,"given":"Doo Sun","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2424-810X","authenticated-orcid":false,"given":"Myung Ho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Gwangju Veterans Hospital, Gwangju 62284, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0192-8161","authenticated-orcid":false,"given":"Young Joon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107667","DOI":"10.1016\/j.carpath.2024.107667","article-title":"Vascular calcification: High incidence sites, distribution, and detection","volume":"72","author":"Gui","year":"2024","journal-title":"Cardiovasc. 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