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J Cell Mol Med. 2017 Nov;21(11):3000-3009. doi: 10.1111/jcmm.13211. Epub 2017 May 29.

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

Author information

1
Heart Failure and Cardiac Regeneration (ICREC) Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain.
2
Center of Regenerative Medicine in Barcelona, Barcelona, Spain.
3
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
4
Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
5
Innovation in Vesicles and Cells for Application in Therapy Group, IGTP, Badalona, Spain.
6
Nephrology Service, Germans Trias i Pujol University Hospital (HUGTiP), Badalona, Spain.
7
Cardiology Service, HUGTiP, Badalona, Spain.
8
Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain.
9
Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain.

Abstract

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 α 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 α chain were assessed in SEC fractions by flow cytometry. LRP1 α 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 α 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.

KEYWORDS:

biomarker; extracellular vesicles; idiopathic dilated cardiomyopathy; sLRP1; size-exclusion chromatography

PMID:
28557183
PMCID:
PMC5661250
DOI:
10.1111/jcmm.13211
[Indexed for MEDLINE]
Free PMC Article

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