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Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy

AuthorsRoura, Santiago; Gálvez-Montón, Carolina; Gonzalo-Calvo, David de; Gámez Valero, Ana; Gastelurrutia, Paloma; Revuelta-López, Elena; Prat-Vidal, Cristina; Soler-Botija, Carolina; Llucià‐Valldeperas, Aida; Perea‐Gil, Isaac; Iborra‐Egea, Oriol; Borràs, Francesc E.; Lupón, Josep; Llorente-Cortés, Vicenta; Bayés Genís, Antoni
Idiopathic dilated cardiomyopathy
Extracellular vesicles
Size-exclusion chromatography
Issue Date29-May-2017
PublisherJohn Wiley & Sons
CitationJournal of Cellular and Molecular Medicine 21(11): 000-3009 (2017)
AbstractIdiopathic dilated cardiomyopathy (IDCM) is a frequent cause of heart transplantation. Potentially valuable blood markers are being sought, andlow-density lipoprotein receptor-related protein 1 (LRP1) has been linked to the underlying molecular basis of the disease. This study comparedcirculating levels of soluble LRP1 (sLRP1) in IDCM patients and healthy controls and elucidated whether sLRP1 is exported out of the myocardiumthrough extracellular vesicles (EVs) to gain a better understanding of the pathogenesis of the disease. LRP1achain expression was analysed insamples collected from the left ventricles of explanted hearts using immunohistochemistry. sLRP1 concentrations were determined in platelet-freeplasma by enzyme-linked immunosorbent assay. Plasma-derived EVs were extracted by size-exclusion chromatography (SEC) and characterizedby nanoparticle tracking analysis and cryo-transmission electron microscopy. The distributions of vesicular (CD9, CD81) and myocardial (caveolin-3) proteins and LRP1achain were assessed in SEC fractions by flow cytometry. LRP1achain was preferably localized to blood vessels in IDCMcompared to control myocardium. Circulating sLRP1 was increased in IDCM patients. CD9- and CD81-positive fractions enriched with membranevesicles with the expected size and morphology were isolated from both groups. The LRP1achain was not present in these SEC fractions, whichwere also positive for caveolin-3. The increase in circulating sLRP1 in IDCM patients may be clinically valuable. Although EVs do not contribute tohigher sLRP1 levels in IDCM, a comprehensive analysis of EV content would provide further insights into the search for novel blood markers
Publisher version (URL)https://doi.org/10.1111/jcmm.13211
Appears in Collections:(IIBB) Artículos
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