Open AccessExtracellular vesicles do not contribute to higher circulating levels of soluble LRP 1 in idiopathic dilated cardiomyopathy
Author(s) -
Roura Santiago,
GálvezMontón Carolina,
GonzaloCalvo David,
Valero Ana Gámez,
Gastelurrutia Paloma,
RevueltaLópez Elena,
PratVidal Cristina,
SolerBotija Carolina,
LluciàValldeperas Aida,
PereaGil Isaac,
IborraEgea Oriol,
Borràs Francesc E.,
Lupón Josep,
LlorenteCortés Vicenta,
BayesGenis Antoni
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13211
Subject(s) - lrp1 , chemistry , nanoparticle tracking analysis , dilated cardiomyopathy , extracellular vesicle , flow cytometry , pathology , pathogenesis , biology , microbiology and biotechnology , lipoprotein , medicine , microvesicles , heart failure , biochemistry , ldl receptor , cholesterol , microrna , gene
Idiopathic dilated cardiomyopathy ( IDCM ) is a frequent cause of heart transplantation. Potentially valuable blood markers are being sought, and low‐density lipoprotein receptor‐related protein 1 ( LRP 1) has been linked to the underlying molecular basis of the disease. This study compared circulating levels of soluble LRP 1 ( sLRP 1) in IDCM patients and healthy controls and elucidated whether sLRP 1 is exported out of the myocardium through extracellular vesicles ( EV s) to gain a better understanding of the pathogenesis of the disease. LRP 1 α chain expression was analysed in samples collected from the left ventricles of explanted hearts using immunohistochemistry. sLRP 1 concentrations were determined in platelet‐free plasma by enzyme‐linked immunosorbent assay. Plasma‐derived EV s were extracted by size‐exclusion chromatography ( SEC ) and characterized by nanoparticle tracking analysis and cryo‐transmission electron microscopy. The distributions of vesicular ( CD 9, CD 81) and myocardial (caveolin‐3) proteins and LRP 1 α chain were assessed in SEC fractions by flow cytometry. LRP 1 α chain was preferably localized to blood vessels in IDCM compared to control myocardium. Circulating sLRP 1 was increased in IDCM patients. CD 9‐ and CD 81‐positive fractions enriched with membrane vesicles with the expected size and morphology were isolated from both groups. The LRP 1 α chain was not present in these SEC fractions, which were also positive for caveolin‐3. The increase in circulating sLRP 1 in IDCM patients may be clinically valuable. Although EV s do not contribute to higher sLRP 1 levels in IDCM , a comprehensive analysis of EV content would provide further insights into the search for novel blood markers.