{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T07:46:37Z","timestamp":1772869597344,"version":"3.50.1"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007697","name":"German Society of Internal Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007697","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Patients with chronic kidney disease (CKD) show a high risk of cardiovascular diseases, predominantly caused by accelerated vascular calcification. Vascular calcification is a highly regulated process with no current treatment. The vasoconstriction-inhibiting factor (VIF) peptide was recently discovered with vasoregulatory properties, but no information regarding calcification has been described.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In the present work, the inhibitory calcification effect of the VIF peptide was analysed in vitro in vascular smooth muscle cells (VSMCs), ex vivo in rat aortic rings, as well as in vivo in rats treated with vitamin D and nicotine (VDN). The VIF peptide inhibits vascular calcification by acting as a calcimimetic for the calcium-sensing receptor, increasing carboxylated matrix Gla protein production and blocking the activation of calcification pathways. The VIF peptide decreased calcium influx, the production of reactive oxygen species, and the activation of multiple kinases in VSMCs. Furthermore, calcium deposition in the aortas of patients with CKD negatively correlates with the VIF peptide concentration. Moreover, we show the cleavage of the VIF peptide from chromogranin-A by \u2018proprotein convertase subtilisin\/kexin type 2\u2019 and \u2018carboxypeptidase E\u2019 enzymes. In addition, \u2018cathepsin K\u2019 degrades the VIF peptide. The active site of the native 35 amino acid-sequence long VIF peptide was identified with seven amino acids, constituting a promising drug candidate with promise for clinical translation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The elucidation of the underlying mechanism by which the VIF peptide inhibits vascular calcification, as well as the active sequence and the cleavage and degradation enzymes, forms the basis for developing preventive and therapeutic measures to counteract vascular calcification.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf016","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T12:32:08Z","timestamp":1741177928000},"page":"507-521","source":"Crossref","is-referenced-by-count":5,"title":["Vasoconstriction-inhibiting factor: an endogenous inhibitor of vascular calcification as a calcimimetic of calcium-sensing receptor"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-1030","authenticated-orcid":false,"given":"Sof\u00eda","family":"de la Puente-Secades","sequence":"first","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]},{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht , Maastricht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3642-7424","authenticated-orcid":false,"given":"Dustin","family":"Mikolajetz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Gayrard","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM) , RD-N\u00e9phrologie and EA7288, Montpellier ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane","family":"Hermann","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shruti","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amina","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7029-4532","authenticated-orcid":false,"given":"\u00c0ngel","family":"Argil\u00e9s","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM) , RD-N\u00e9phrologie and EA7288, Montpellier 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,","place":["Germany"]},{"name":"Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), University Hospital RWTH Aachen , Aachen ,","place":["Germany"]},{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich , Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuojun","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3053-6984","authenticated-orcid":false,"given":"Heidi","family":"Noels","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiovascular Research (IMCAR), University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30 , Aachen 52074 ,","place":["Germany"]},{"name":"Aachen-Maastricht Institute for CardioRenal Disease 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