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Potentially valuable blood markers are being sought, and low\u2010density lipoprotein receptor\u2010related protein 1 (<jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1) has been linked to the underlying molecular basis of the disease. This study compared circulating levels of soluble <jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1 (<jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1) in <jats:styled-content style=\"fixed-case\">IDCM<\/jats:styled-content> patients and healthy controls and elucidated whether <jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1 is exported out of the myocardium through extracellular vesicles (<jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>s) to gain a better understanding of the pathogenesis of the disease. <jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1 \u03b1 chain expression was analysed in samples collected from the left ventricles of explanted hearts using immunohistochemistry. <jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1 concentrations were determined in platelet\u2010free plasma by enzyme\u2010linked immunosorbent assay. Plasma\u2010derived <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>s were extracted by size\u2010exclusion chromatography (<jats:styled-content style=\"fixed-case\">SEC<\/jats:styled-content>) and characterized by nanoparticle tracking analysis and cryo\u2010transmission electron microscopy. The distributions of vesicular (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>9, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>81) and myocardial (caveolin\u20103) proteins and <jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1 \u03b1 chain were assessed in <jats:styled-content style=\"fixed-case\">SEC<\/jats:styled-content> fractions by flow cytometry. <jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1 \u03b1 chain was preferably localized to blood vessels in <jats:styled-content style=\"fixed-case\">IDCM<\/jats:styled-content> compared to control myocardium. Circulating <jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1 was increased in <jats:styled-content style=\"fixed-case\">IDCM<\/jats:styled-content> patients. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>9\u2010 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>81\u2010positive fractions enriched with membrane vesicles with the expected size and morphology were isolated from both groups. The <jats:styled-content style=\"fixed-case\">LRP<\/jats:styled-content>1 \u03b1 chain was not present in these <jats:styled-content style=\"fixed-case\">SEC<\/jats:styled-content> fractions, which were also positive for caveolin\u20103. The increase in circulating <jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1 in <jats:styled-content style=\"fixed-case\">IDCM<\/jats:styled-content> patients may be clinically valuable. Although <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content>s do not contribute to higher <jats:styled-content style=\"fixed-case\">sLRP<\/jats:styled-content>1 levels in <jats:styled-content style=\"fixed-case\">IDCM<\/jats:styled-content>, a comprehensive analysis of <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content> content would provide further insights into the search for novel blood markers.<\/jats:p>","DOI":"10.1111\/jcmm.13211","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T04:56:36Z","timestamp":1496120196000},"page":"3000-3009","source":"Crossref","is-referenced-by-count":11,"title":["Extracellular vesicles do not contribute to higher circulating levels of soluble <scp>LRP<\/scp>1 in idiopathic dilated 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