Altres ajuts: Fundació La MARATÓ de TV3 (201502, 201516, 201521_10); Fundació Daniel Bravo Andreu; Sociedad Espanola de Cardiologıa; Societat Catalana de Cardiologia; Generalitat de Catalunya (SGR 2014, CERCA Programme); Fundació Bancaria La Caixa; Red de Terapia Celular TerCel (RD16/0011/0006); CIBER Cardiovascular (CB16/11/00403)

Idiopathic dilated cardiomyopathy () is a frequent cause of heart transplantation. Potentially valuable blood markers are being sought, and low-density lipoprotein receptor-related protein 1 (1) has been linked to the underlying molecular basis of the disease. This study compared circulating levels of soluble 1 (1) in patients and healthy controls and elucidated whether 1 is exported out of the myocardium through extracellular vesicles (s) to gain a better understanding of the pathogenesis of the disease. 1 α chain expression was analysed in samples collected from the left ventricles of explanted hearts using immunohistochemistry. 1 concentrations were determined in platelet-free plasma by enzyme-linked immunosorbent assay. Plasma-derived s were extracted by size-exclusion chromatography () and characterized by nanoparticle tracking analysis and cryo-transmission electron microscopy. The distributions of vesicular (9, 81) and myocardial (caveolin-3) proteins and 1 α chain were assessed in fractions by flow cytometry. 1 α chain was preferably localized to blood vessels in compared to control myocardium. Circulating 1 was increased in patients. 9- and 81-positive fractions enriched with membrane vesicles with the expected size and morphology were isolated from both groups. The 1 α chain was not present in these fractions, which were also positive for caveolin-3. The increase in circulating 1 in patients may be clinically valuable. Although s do not contribute to higher 1 levels in , a comprehensive analysis of content would provide further insights into the search for novel blood markers.