{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T10:26:41Z","timestamp":1778408801105,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular remodelling is an essential pathophysiological state in many circulatory diseases. Abnormal vascular smooth muscle cell (VSMC) behaviour leads to neointimal formation and may eventually results in major adverse cardiovascular events. The C1q\/TNF\u2010related protein (C1QTNF) family is closely associated with cardiovascular disease. Notably, C1QTNF4 has unique two C1q domains. However, the role of C1QTNF4 in vascular diseases remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C1QTNF4 expression was detected in human serum and artery tissues using ELISA and multiplex immunofluorescence (mIF) staining. Scratch assay, transwell assay and confocal microscopy were used to investigate C1QTNF4 effects on VSMC migration. EdU incorporation, MTT assay and cell counting experiment revealed C1QTNF4 effects on VSMC proliferation. C1QTNF4\u2010transgenic, C1QTNF4<jats:sup>\u2212\/\u2212<\/jats:sup> and AAV9\u2010mediated VSMC\u2010specific C1QTNF4 restoration C1QTNF4<jats:sup>\u2212\/\u2010<\/jats:sup> mouse and rat disease models were generated. RNA\u2010seq, quantitative real\u2010time PCR, western blot, mIF, proliferation and migration assays were used to investigate the phenotypic characteristics and underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum C1QTNF4 levels were decreased in patients with arterial stenosis. C1QTNF4 shows colocalisation with VSMC in human renal arteries. In vitro, C1QTNF4 inhibits VSMC proliferation and migration and alters VSMC phenotype. In vivo, an adenovirus\u2010infected rat balloon injury model, C1QTNF4\u2010transgenic and C1QTNF4<jats:sup>\u2212\/\u2212<\/jats:sup> mouse wire\u2010injury models with or without VSMC\u2010specific C1QTNF4 restoration were established to mimic the VSMC repair and remodelling. The results show that C1QTNF4 decreases intimal hyperplasia. Especially, we displayed the rescue effect of C1QTNF4 in vascular remodelling using AAV vectors. Next, transcriptome analysis of artery tissue identified the potential mechanism. In vitro and in vivo experiments confirm that C1QTNF4 ameliorates neointimal formation and maintains vascular morphology by downregulating the FAK\/PI3K\/AKT pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that C1QTNF4 is a novel inhibitor of VSMC proliferation and migration that acts by downregulating the FAK\/PI3K\/AKT pathway, thus protecting blood vessels from abnormal neointima formation. These results provide new insights into promising potent treatments for vascular stenosis diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1261","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T04:09:19Z","timestamp":1684901359000},"source":"Crossref","is-referenced-by-count":10,"title":["C1q\/TNF\u2010related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-9569","authenticated-orcid":false,"given":"Jingying","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, The lnstitute of Cardiovascular Sciences, School of Basic Medical Sciences Peking University Health Science Center  Beijing China"},{"name":"Department of Cardiology Fuwai Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for 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