{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:51:37Z","timestamp":1780080697592,"version":"3.54.0"},"reference-count":27,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/501100001809","name":"national nature science foundation of China","doi-asserted-by":"crossref","award":["81600374"],"award-info":[{"award-number":["81600374"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:p> Vascular smooth muscle cell (SMC) phenotypic modulation contributes to the development of restenosis. A sorafenib-eluting stent was specifically designed to target SMC phenotypic modulation to inhibit in-stent restenosis in the present study. SMC contractile protein from the freshly isolated rat aorta was expressed at a high level, but its expression was dramatically reduced after SMCs were cultured in 10% FBS for 1 wk. After sorafenib treatment, SMC contractile protein expression was markedly upregulated. We further observed that Yes-associated protein (YAP) expression was attenuated after sorafenib treatment in a dose-dependent manner. Overexpression of YAP by lentivirus reversed the expression of sorafenib-induced SMC contractile protein and increased the expression of cyclin D. Mechanistically, sorafenib regulated the serum response factor-myocardin (SRF-Myocd) complex through competitive binding of YAP to Myocd and increased SRF binding to CArG-containing regions of SMC-specific contractile genes within intact chromatin, thereby controlling the activity of smooth muscle-specific gene transcription. In a rabbit carotid model, the sorafenib-eluting stent (SFES) dramatically inhibited in-stent restenosis and upregulated SMC contractile protein expression. Overexpression of YAP blocked the antirestenosis effect of SFES and repressed contractile smooth muscle-specific genes in vivo, indicating that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. We demonstrated that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. Targeting SMC phenotypic modulation by drug-eluting stent represents an attractive therapeutic approach for the treatment of occlusive vascular diseases. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY In the present study, we demonstrated that sorafenib regulates smooth muscle cell (SMC) phenotypic modulation from a proliferative to a contractile state. Sorafenib induced a myocardin-serum response factor interaction and increased SMC contractile gene transcription through the Yes-associated protein pathway. Moreover, local delivery of sorafenib regulating SMC phenotypic modulation represents a promising strategy in the design of drug-eluting stents. <\/jats:p>","DOI":"10.1152\/ajpheart.00089.2019","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T10:44:32Z","timestamp":1562928272000},"page":"H541-H551","source":"Crossref","is-referenced-by-count":14,"title":["Drug-eluting stent specifically designed to target vascular smooth muscle cell phenotypic modulation attenuated restenosis through the YAP pathway"],"prefix":"10.1152","volume":"317","author":[{"given":"Chen","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Affiliated Hospital of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University Medical School, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14079"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.243212"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-18-00024"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026046"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.425"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305863"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2018.12.020"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5986"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2018.04.073"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw253"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31827efd9e"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2018.04.014"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25679"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309322"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00386.2006"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23966"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2015.09.041"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.269811"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.108.789974"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3866"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25208"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4244\/EIJV13I14A262"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.254730"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.329268"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305748"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1843810"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.308992"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00089.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:06:28Z","timestamp":1567962388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00089.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,1]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,9,1]]}},"alternative-id":["10.1152\/ajpheart.00089.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00089.2019","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,1]]}}}