{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:14:36Z","timestamp":1784729676374,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014138","name":"Centre for Individualized Medicine in Arterial Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014138","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["0064142"],"award-info":[{"award-number":["0064142"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["0075258"],"award-info":[{"award-number":["0075258"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","award":["2034-00136B"],"award-info":[{"award-number":["2034-00136B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011076","name":"Simon Fougner Hartmanns Familiefond","doi-asserted-by":"publisher","award":["2023-0066"],"award-info":[{"award-number":["2023-0066"]}],"id":[{"id":"10.13039\/501100011076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006356","name":"University of Southern Denmark","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015223","name":"Danish Diabetes Academy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015223","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidaemic conditions. Inducing hyperlipidaemia in both models resulted in severe aorta malformation and a 17-fold increase in atherosclerosis formation. Lipid-rich lesions developed at sites of the vasculature typically protected from atherosclerosis development by laminar blood flow, covering 90% of aortas and extending to other vessels, including coronary arteries. Evaluation at earlier time points revealed medial lipid accumulation as a lesion-initiating event. Fluorescently labelled LDL injection followed by confocal microscopy showed increased LDL retention in the medial layer of Ccn2 knockout aortas, likely attributed to marked proteoglycan enrichment of the medial extracellular matrix. Analyses leveraging data from the Athero-Express study cohort indicated the relevance of CCN2 in established human lesions, as CCN2 correlated with SMC marker transcripts across 654 transcriptomically profiled carotid plaques. These findings were substantiated through in situ hybridization showing CCN2 expression predominantly in the fibrous cap.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study identifies CCN2 as a major constituent of the normal artery wall, critical in regulating SMC differentiation and aorta integrity and possessing a protective role against atherosclerosis development. These findings underscore the need for further investigation into the potential effects of anti-CCN2-based therapies on the vasculature.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae174","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T01:58:21Z","timestamp":1724291901000},"page":"1851-1868","source":"Crossref","is-referenced-by-count":3,"title":["Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis"],"prefix":"10.1093","volume":"120","author":[{"given":"Jannik H","family":"Larsen","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark , Campusvej 55, DK-5230 Odense M ,","place":["Denmark"]},{"name":"Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital , J. B. 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Winsl\u00f8ws Vej 4, DK-5000 Odense C ,","place":["Denmark"]},{"name":"Department of Cardiothoracic and Vascular Surgery, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla S","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark , Campusvej 55, DK-5230 Odense M ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-8457","authenticated-orcid":false,"given":"Andrietta","family":"Grentzmann","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark , Campusvej 55, DK-5230 Odense M ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bloksgaard","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark , Campusvej 55, DK-5230 Odense M ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boye L","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark , Campusvej 55, DK-5230 Odense M ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal R","family":"Rodriguez-D\u00edez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Complutense University School of Medicine , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ruiz-Ortega","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz-Universidad Aut\u00f3noma Madrid , Madrid 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