{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:54:59Z","timestamp":1760234099965,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.<\/jats:p>","DOI":"10.3390\/ma14081970","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T15:30:39Z","timestamp":1618414239000},"page":"1970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High Magnesium and Sirolimus on Rabbit Vascular Cells\u2014An In Vitro Proof of Concept"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-6299","authenticated-orcid":false,"given":"Giorgia","family":"Fedele","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences L. Sacco, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-9891","authenticated-orcid":false,"given":"Sara","family":"Castiglioni","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences L. Sacco, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette A.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences L. Sacco, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"},{"name":"Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa), Universit\u00e0 di Milano, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-7825","authenticated-orcid":false,"given":"Laura","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences L. Sacco, Universit\u00e0 di Milano, Via GB Grassi 74, 20157 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCRESAHA.117.308903","article-title":"Reducing the global burden of cardiovascular disease, part 1: The epidemiology and risk factors","volume":"121","author":"Joseph","year":"2017","journal-title":"Circ. 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