Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy
Por:
Roura, S, Galvez-Monton, C, de Gonzalo-Calvo, D, Valero, AG, Gastelurrutia, P, Revuelta-Lopez, E, Prat-Vidal, C, Soler-Botija, C, Llucia-Valldeperas, A, Perea-Gil, I, Iborra-Egea, O, Borras, FE, Lupon, J, Llorente-Cortes, V, Bayes-Genis, A
Publicada:
1 nov 2017
Resumen:
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 (LRP1) has been linked to the underlying molecular basis of the disease. This study compared circulating levels of soluble LRP1 (sLRP1) in IDCM patients and healthy controls and elucidated whether sLRP1 is exported out of the myocardium through extracellular vesicles (EVs) to gain a better understanding of the pathogenesis of the disease. LRP1 alpha chain expression was analysed in samples collected from the left ventricles of explanted hearts using immunohistochemistry. sLRP1 concentrations were determined in platelet-free plasma by enzyme-linked immunosorbent assay. Plasma-derived EVs were extracted by size-exclusion chromatography (SEC) and characterized by nanoparticle tracking analysis and cryo-transmission electron microscopy. The distributions of vesicular (CD9, CD81) and myocardial (caveolin-3) proteins and LRP1 alpha chain were assessed in SEC fractions by flow cytometry. LRP1 alpha chain was preferably localized to blood vessels in IDCM compared to control myocardium. Circulating sLRP1 was increased in IDCM patients. CD9- and CD81-positive fractions enriched with membrane vesicles with the expected size and morphology were isolated from both groups. The LRP1 alpha chain was not present in these SEC fractions, which were also positive for caveolin-3. The increase in circulating sLRP1 in IDCM patients may be clinically valuable. Although EVs do not contribute to higher sLRP1 levels in IDCM, a comprehensive analysis of EV content would provide further insights into the search for novel blood markers.
Filiaciones:
Roura, S:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Ctr Regenerat Med Barcelona, Barcelona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Galvez-Monton, C:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
de Gonzalo-Calvo, D:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Hosp Santa Creu & Sant Pau, Cardiovasc Res Ctr, CSIC ICCC, IIB St Pau, Barcelona, Spain
Valero, AG:
IGTP, Innovat Vesicles & Cells Applicat Therapy Grp, Badalona, Spain
Gastelurrutia, P:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Revuelta-Lopez, E:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Prat-Vidal, C:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Soler-Botija, C:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Llucia-Valldeperas, A:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Perea-Gil, I:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Iborra-Egea, O:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Borras, FE:
IGTP, Innovat Vesicles & Cells Applicat Therapy Grp, Badalona, Spain
Germans Trias & Pujol Univ Hosp HUGTiP, Nephrol Serv, Badalona, Spain
Lupon, J:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
HUGTiP, Cardiol Serv, Badalona, Spain
Barcelona Autonomous Univ UAB, Dept Med, Barcelona, Spain
Llorente-Cortes, V:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Hosp Santa Creu & Sant Pau, Cardiovasc Res Ctr, CSIC ICCC, IIB St Pau, Barcelona, Spain
CSIC, Inst Biomed Res Barcelona IIBB, Barcelona, Spain
Bayes-Genis, A:
Hlth Sci Res Inst Germans Trias & Pujol IGTP, Heart Failure & Cardiac Regenerat ICREC Res Progr, Badalona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
HUGTiP, Cardiol Serv, Badalona, Spain
Barcelona Autonomous Univ UAB, Dept Med, Barcelona, Spain
Gold, Green Published
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