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In diabetes mellitus type 2 (T2DM), the expression of endothelin (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>)\u20101 is increased. As treatment with an <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 antagonists affects <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> levels <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> in patients with T2DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> study: Human umbilical vein endothelial cells (<jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>) were stimulated with <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 alone and <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 in combination with a dual <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010A and <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u2010B endothelin receptor blocker. <jats:italic>In vivo<\/jats:italic> study: Patients with T2DM were randomized to treatment with the <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> receptor antagonist bosentan or placebo. After 4 weeks, the patients were re\u2010examined and blood samples were obtained. <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> counts in supernatants and plasma samples were determined using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> study: In supernatants of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101\u2010stimulated <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s, the increased release of <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> was reduced significantly by co\u2010incubation with an <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 receptor antagonist (e.g. CD31+\/CD42b\u2010<jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> decreased from 37\u00b71% \u00b1 2\u00b78 to 31\u00b75% \u00b1 2\u00b78 SEM, <jats:italic>P<\/jats:italic> = 0\u00b70078). <jats:italic>In vivo<\/jats:italic> study: No changes in <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> levels in blood samples of patients with T2DM were found after 4 weeks of bosentan treatment (<jats:italic>n<\/jats:italic> = 36, <jats:italic>P<\/jats:italic> = <jats:italic>ns<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our <jats:italic>in vitro<\/jats:italic> results suggest that <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 stimulates the release of <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s via a receptor\u2010dependent mechanism. Co\u2010incubation with an endothelin receptor blocker abolished <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101\u2010dependent <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> release. However, treatment with bosentan for 4 weeks failed to alter <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> levels in patients with T2DM. Other factors seem to have influenced <jats:styled-content style=\"fixed-case\">EMP<\/jats:styled-content> release in patients with T2DM independent of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 receptor\u2010mediated mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12652","type":"journal-article","created":{"date-parts":[[2016,6,20]],"date-time":"2016-06-20T15:12:23Z","timestamp":1466435543000},"page":"707-713","source":"Crossref","is-referenced-by-count":8,"title":["Effect of endothelin\u20101 and endothelin receptor blockade on the release of microparticles"],"prefix":"10.1111","volume":"46","author":[{"given":"Christian","family":"Jung","sequence":"first","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine Medical Faculty University Duesseldorf Duesseldorf Germany"},{"name":"Division of Cardiology Department of Medicine Karolinska Institutet Karolinska University Hospital Stockholm 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