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In the present study, we investigated the role of vascular Vasn expression on vascular function. We used inducible <jats:italic>Vasn<\/jats:italic> knockout mice (<jats:italic>Vasn<\/jats:italic><jats:sup>CRE\u2010ERT KO<\/jats:sup> and <jats:italic>Vasn<\/jats:italic><jats:sup>SMMHC\u2010CRE\u2010ERT2 KO<\/jats:sup>, in which respectively all cells or SMCs only are targeted) to analyze the consequences of total or selective Vasn loss on vascular function. Furthermore, in vivo effects were investigated in vitro using human VSMCs. The death of <jats:italic>Vasn<\/jats:italic><jats:sup>CRE\u2010ERT KO<\/jats:sup> mice 21 days after tamoxifen injection was concomitant with decreases in blood pressure, angiotensin II levels, and vessel contractibility to phenylephrine. The <jats:italic>Vasn<\/jats:italic><jats:sup>SMMHC\u2010CRE\u2010ERT2 KO<\/jats:sup> mice displayed concomitant changes in vessel contractibility in response to phenylephrine and angiotensin II levels. In vitro, <jats:italic>VASN<\/jats:italic> deficiency was associated with a shift toward the SMC contractile phenotype, an increase in basal intracellular Ca<jats:sup>2+<\/jats:sup> levels, and a decrease in the SMCs' ability to generate a calcium signal in response to carbachol or phenylephrine. Additionally, impaired endothelium\u2010dependent relaxation (due to changes in nitric oxide signaling) was observed in all <jats:italic>Vasn<\/jats:italic> knockout mice models. Our present findings highlight the role played by Vasn SMC expression in the maintenance of vascular functions. The mechanistic experiments suggested that these effects are mediated by SMC phenotype switching and changes in intracellular calcium homeostasis, angiotensin II levels, and NO signaling.<\/jats:p>","DOI":"10.1002\/jcp.30838","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T06:53:40Z","timestamp":1658904820000},"page":"3845-3859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Vasorin plays a critical role in vascular smooth muscle cells and arterial functions"],"prefix":"10.1002","volume":"237","author":[{"given":"Lo\u00efc","family":"Louvet","sequence":"first","affiliation":[{"name":"UR 7517 UPJV, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications (MP3CV) Picardie Jules Verne University Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga\u00eblle","family":"Lenglet","sequence":"additional","affiliation":[{"name":"UR 7517 UPJV, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications (MP3CV) Picardie Jules Verne University Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Michaela","family":"Krautzberger","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3993-1561","authenticated-orcid":false,"given":"Romuald","family":"Mentaverri","sequence":"additional","affiliation":[{"name":"UR 7517 UPJV, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications (MP3CV) Picardie Jules Verne University Amiens France"},{"name":"Amiens University Hospital Human Biology Center Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Hague","sequence":"additional","affiliation":[{"name":"UR EA4667, UPJV, Laboratoire de Physiologie Cellulaire et Mol\u00e9culaire Picardie Jules Verne University Amiens 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m\u00e9decine bucco\u2010dentaire (GH Sorbonne Universit\u00e9, GH Paris Nord Universit\u00e9 de Paris, GH Henri Mondor) Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Andrique","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, URP2496 F\u201092120 Montrouge France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Gaucher","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, URP2496 F\u201092120 Montrouge France"},{"name":"AP\u2010HP, FHU DDS\u2010net, Services de m\u00e9decine bucco\u2010dentaire (GH Sorbonne Universit\u00e9, GH Paris Nord Universit\u00e9 de Paris, GH Henri Mondor) Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy","family":"Gomila","sequence":"additional","affiliation":[{"name":"UR 7517 UPJV, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications (MP3CV) Picardie 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