In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 11 ( 2017-11), p. 3000-3009
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 ( 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.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2017.21.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2076114-4
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