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

Santiago Roura, Carolina Gálvez-Montón, David de Gonzalo-Calvo, Ana Gámez Valero, Paloma Gastelurrutia, Elena Revuelta-López, Cristina Prat-Vidal, Carolina Soler-Botija, Aida Llucià-Valldeperas, Isaac Perea-Gil, Oriol Iborra-Egea, Francesc E Borràs, Josep Lupón, Vicenta Llorente-Cortés, Antoni Bayes-Genis

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)3000-3009
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 2017

Cite this

Roura, S., Gálvez-Montón, C., de Gonzalo-Calvo, D., Valero, A. G., Gastelurrutia, P., Revuelta-López, E., ... Bayes-Genis, A. (2017). Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy. Journal of Cellular and Molecular Medicine, 21(11), 3000-3009. https://doi.org/10.1111/jcmm.13211
Roura, Santiago ; Gálvez-Montón, Carolina ; de Gonzalo-Calvo, David ; Valero, Ana Gámez ; 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 ; Bayes-Genis, Antoni. / Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy. In: Journal of Cellular and Molecular Medicine. 2017 ; Vol. 21, No. 11. pp. 3000-3009.
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title = "Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy",
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.",
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author = "Santiago Roura and Carolina G{\'a}lvez-Mont{\'o}n and {de Gonzalo-Calvo}, David and Valero, {Ana G{\'a}mez} and Paloma Gastelurrutia and Elena Revuelta-L{\'o}pez and Cristina Prat-Vidal and Carolina Soler-Botija and Aida Lluci{\`a}-Valldeperas and Isaac Perea-Gil and Oriol Iborra-Egea and Borr{\`a}s, {Francesc E} and Josep Lup{\'o}n and Vicenta Llorente-Cort{\'e}s and Antoni Bayes-Genis",
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Roura, S, Gálvez-Montón, C, de Gonzalo-Calvo, D, Valero, AG, Gastelurrutia, P, Revuelta-López, E, Prat-Vidal, C, Soler-Botija, C, Llucià-Valldeperas, A, Perea-Gil, I, Iborra-Egea, O, Borràs, FE, Lupón, J, Llorente-Cortés, V & Bayes-Genis, A 2017, 'Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy' Journal of Cellular and Molecular Medicine, vol. 21, no. 11, pp. 3000-3009. https://doi.org/10.1111/jcmm.13211

Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy. / Roura, Santiago; Gálvez-Montón, Carolina; de Gonzalo-Calvo, David; Valero, Ana Gámez; 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; Bayes-Genis, Antoni.

In: Journal of Cellular and Molecular Medicine, Vol. 21, No. 11, 11.2017, p. 3000-3009.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy

AU - Roura, Santiago

AU - Gálvez-Montón, Carolina

AU - de Gonzalo-Calvo, David

AU - Valero, Ana Gámez

AU - Gastelurrutia, Paloma

AU - Revuelta-López, Elena

AU - Prat-Vidal, Cristina

AU - Soler-Botija, Carolina

AU - Llucià-Valldeperas, Aida

AU - Perea-Gil, Isaac

AU - Iborra-Egea, Oriol

AU - Borràs, Francesc E

AU - Lupón, Josep

AU - Llorente-Cortés, Vicenta

AU - Bayes-Genis, Antoni

N1 - © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Aged

KW - Biomarkers/blood

KW - Cardiomyopathy, Dilated/blood

KW - Case-Control Studies

KW - Caveolin 3/blood

KW - Extracellular Vesicles/chemistry

KW - Female

KW - Gene Expression Regulation

KW - Heart Transplantation

KW - Heart Ventricles/metabolism

KW - Humans

KW - Low Density Lipoprotein Receptor-Related Protein-1/blood

KW - Male

KW - Middle Aged

KW - Myocardium/metabolism

KW - Tetraspanin 28/blood

KW - Tetraspanin 29/blood

U2 - 10.1111/jcmm.13211

DO - 10.1111/jcmm.13211

M3 - Article

VL - 21

SP - 3000

EP - 3009

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-4934

IS - 11

ER -

Roura S, Gálvez-Montón C, de Gonzalo-Calvo D, Valero AG, Gastelurrutia P, Revuelta-López E et al. Extracellular vesicles do not contribute to higher circulating levels of soluble LRP1 in idiopathic dilated cardiomyopathy. Journal of Cellular and Molecular Medicine. 2017 Nov;21(11):3000-3009. https://doi.org/10.1111/jcmm.13211