{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:13:06Z","timestamp":1789038786926,"version":"build-2803163510"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2026AFC1014"],"award-info":[{"award-number":["2026AFC1014"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2025AFB260"],"award-info":[{"award-number":["2025AFB260"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Cardiovasc. Dev. Dis.","JCDD"],"abstract":"<jats:p>Chronic venous disease (CVD) is a prevalent peripheral vascular disorder characterized by vascular remodeling driven by hemodynamic overload, yet available animal models are limited by high surgical difficulty and unstable induction efficiency. Here, we developed a novel mouse venous high-load remodeling model by selectively ablating the unilateral cervical venous drainage system. After 4 weeks, compensatory contralateral jugular veins were assessed via ultrasonography, histology, Western blot, and bulk RNA sequencing. The model displayed marked luminal dilation, wall hypertrophy, and excessive collagen deposition, along with downregulated smooth muscle contractile markers (\u03b1-SMA, SM22\u03b1) and upregulated adhesion molecule ICAM-1. Transcriptomic profiling identified 252 differentially expressed genes, predominantly enriched in extracellular matrix organization, angiogenesis, and complement-coagulation cascades, suggesting potential pathways involved in the venous remodeling process. This model reliably recapitulates the pathological features associated with hemodynamic overload-induced venous remodeling, offering a valuable tool for investigating CVD pathogenesis and intervention targets.<\/jats:p>","DOI":"10.3390\/jcdd13090452","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:27:21Z","timestamp":1789036041000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Mouse Model for Venous High-Load Remodeling Induced by Unilateral Jugular Vein Transection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-5425","authenticated-orcid":false,"given":"Ke","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Shiwen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Peng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Wangxuan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Junfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Junli","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Shunchang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Experimental Animals, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9626-8410","authenticated-orcid":false,"given":"Hongping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12325-019-0881-7","article-title":"The Seriousness of Chronic Venous Disease: A Review of Real-World Evidence","volume":"36","author":"Davies","year":"2019","journal-title":"Adv. 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Surg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Smetanina, M.A., Korolenya, V.A., Kel, A.E., Sevostyanova, K.S., Gavrilov, K.A., Shevela, A.I., and Filipenko, M.L. (2023). Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress. Epigenomes, 7.","DOI":"10.3390\/epigenomes7010008"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s100169910092","article-title":"Expression of adhesion molecules and cytokines on saphenous veins in chronic venous insufficiency","volume":"14","author":"Takase","year":"2000","journal-title":"Ann. Vasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.2147\/OTT.S244128","article-title":"GPR30 Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells via Activating the AKT and ERK Pathways","volume":"13","author":"Zha","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3892\/mmr.2021.12266","article-title":"MicroRNA-199a-5p regulates FOXC2 to control human vascular smooth muscle cell phenotypic switch","volume":"24","author":"Cao","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S1078-5884(98)80039-7","article-title":"Endothelial activation in patients with chronic venous disease","volume":"15","author":"Saharay","year":"1998","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_10","first-page":"6475","article-title":"IQGAP1 promotes the phenotypic switch of vascular smooth muscle by myocardin pathway: A potential target for varicose vein","volume":"7","author":"Huang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"845","DOI":"10.3892\/etm.2015.2170","article-title":"Expression and significance of NELIN and SM22\u03b1 in varicose vein tissue","volume":"9","author":"Chen","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1024\/0301-1526.34.3.170","article-title":"Histopathological changes and expression of adhesion molecules and laminin in varicose veins","volume":"34","author":"Aunapuu","year":"2005","journal-title":"Vasa"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hounkpe, B.W., Benatti, R.O., Carvalho, B.S., and De Paula, E.V. (2020). Identification of common and divergent gene expression signatures in patients with venous and arterial thrombosis using data from public repositories. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235501"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1024\/0301-1526.30.3.184","article-title":"Coagulation and fibrinolysis in chronic venous insufficiency","volume":"30","author":"Blomgren","year":"2001","journal-title":"Vasa"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/imr.12471","article-title":"Dangerous liaisons: Complement, coagulation, and kallikrein\/kinin cross-talk act as a linchpin in the events leading to thromboinflammation","volume":"274","author":"Ekdahl","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/00033197241256680","article-title":"Vicious Circle With Venous Hypertension, Irregular Flow, Pathological Venous Wall Remodeling, and Valve Destruction in Chronic Venous Disease: A Review","volume":"77","author":"Nadasy","year":"2026","journal-title":"Angiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/cvr\/cvw075","article-title":"Extracellular matrix remodelling in response to venous hypertension: Proteomics of human varicose veins","volume":"110","author":"Oklu","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1016\/j.jvs.2009.01.070","article-title":"Characterization of a porcine model of chronic superficial varicose veins","volume":"49","author":"Jones","year":"2009","journal-title":"J. Vasc. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.ejvs.2018.02.009","article-title":"Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension","volume":"55","author":"Cyrino","year":"2018","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1096\/fj.11-185975","article-title":"Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1","volume":"25","author":"Feldner","year":"2011","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17820","DOI":"10.1038\/s41598-017-17910-0","article-title":"Magnolol inhibits venous remodeling in mice","volume":"7","author":"Kuk","year":"2017","journal-title":"Sci. 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