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Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells

Atherosclerosis and cardiovascular disease development is the outcome of intermediate processes where endothelial dysfunction and vascular inflammation are main protagonists. Cell-derived microvesicles (MVs), endothelial progenitor cells (EPCs), and circulating microRNAs (miRNAs) are known as biomar...

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Autores principales: Alexandru, Nicoleta, Andrei, Eugen, Safciuc, Florentina, Dragan, Emanuel, Balahura, Ana Maria, Badila, Elisabeta, Georgescu, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072151/
https://www.ncbi.nlm.nih.gov/pubmed/32059493
http://dx.doi.org/10.3390/cells9020423
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author Alexandru, Nicoleta
Andrei, Eugen
Safciuc, Florentina
Dragan, Emanuel
Balahura, Ana Maria
Badila, Elisabeta
Georgescu, Adriana
author_facet Alexandru, Nicoleta
Andrei, Eugen
Safciuc, Florentina
Dragan, Emanuel
Balahura, Ana Maria
Badila, Elisabeta
Georgescu, Adriana
author_sort Alexandru, Nicoleta
collection PubMed
description Atherosclerosis and cardiovascular disease development is the outcome of intermediate processes where endothelial dysfunction and vascular inflammation are main protagonists. Cell-derived microvesicles (MVs), endothelial progenitor cells (EPCs), and circulating microRNAs (miRNAs) are known as biomarkers and potential regulators for atherosclerotic vascular disease, but their role in the complexity of the inflammatory process and in the mechanism of vascular restoration is far from clear. We aimed to evaluate the biological activity and functional role of MVs, in particular of the EPCs-derived MVs (MVEs), of healthy origins in reducing atherosclerotic vascular disease development. The experiments were performed on hamsters divided into the following groups: simultaneously hypertensive–hyperlipidemic (HH group) by combining two feeding conditions for 4 months; HH with retro-orbital sinus injection containing 1 × 10(5) MVs or MVEs from control hamsters, one dose per month for 4 months of HH diet, to prevent atherosclerosis (HH-MVs or HH-MVEs group); and controls (C group), age-matched normal healthy animals. We found that circulating MV and MVE transplantation of healthy origins significantly reduces atherosclerosis development via (1) the mitigation of dyslipidemia, hypertension, and circulating EPC/cytokine/chemokine levels and (2) the structural and functional remodeling of arterial and left ventricular walls. We also demonstrated that (1) circulating MVs contain miRNAs; this was demonstrated by validating MVs and MVEs as transporters of Ago2-miRNA, Stau1-miRNA, and Stau2-miRNA complexes and (2) MV and MVE administration significantly protect against atherosclerotic cardiovascular disease via transfer of miR-223, miR-21, miR-126, and miR-146a to circulating late EPCs. It should be mentioned that the favorable effects of MVEs were greater than those of MVs. Our findings suggest that allogenic MV and MVE administration of healthy origins could counteract HH diet-induced detrimental effects by biologically active miR-10a, miR-21, miR-126, and miR-146a transfer to circulating EPCs, mediating their vascular repair function in atherosclerosis processes.
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spelling pubmed-70721512020-03-19 Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells Alexandru, Nicoleta Andrei, Eugen Safciuc, Florentina Dragan, Emanuel Balahura, Ana Maria Badila, Elisabeta Georgescu, Adriana Cells Article Atherosclerosis and cardiovascular disease development is the outcome of intermediate processes where endothelial dysfunction and vascular inflammation are main protagonists. Cell-derived microvesicles (MVs), endothelial progenitor cells (EPCs), and circulating microRNAs (miRNAs) are known as biomarkers and potential regulators for atherosclerotic vascular disease, but their role in the complexity of the inflammatory process and in the mechanism of vascular restoration is far from clear. We aimed to evaluate the biological activity and functional role of MVs, in particular of the EPCs-derived MVs (MVEs), of healthy origins in reducing atherosclerotic vascular disease development. The experiments were performed on hamsters divided into the following groups: simultaneously hypertensive–hyperlipidemic (HH group) by combining two feeding conditions for 4 months; HH with retro-orbital sinus injection containing 1 × 10(5) MVs or MVEs from control hamsters, one dose per month for 4 months of HH diet, to prevent atherosclerosis (HH-MVs or HH-MVEs group); and controls (C group), age-matched normal healthy animals. We found that circulating MV and MVE transplantation of healthy origins significantly reduces atherosclerosis development via (1) the mitigation of dyslipidemia, hypertension, and circulating EPC/cytokine/chemokine levels and (2) the structural and functional remodeling of arterial and left ventricular walls. We also demonstrated that (1) circulating MVs contain miRNAs; this was demonstrated by validating MVs and MVEs as transporters of Ago2-miRNA, Stau1-miRNA, and Stau2-miRNA complexes and (2) MV and MVE administration significantly protect against atherosclerotic cardiovascular disease via transfer of miR-223, miR-21, miR-126, and miR-146a to circulating late EPCs. It should be mentioned that the favorable effects of MVEs were greater than those of MVs. Our findings suggest that allogenic MV and MVE administration of healthy origins could counteract HH diet-induced detrimental effects by biologically active miR-10a, miR-21, miR-126, and miR-146a transfer to circulating EPCs, mediating their vascular repair function in atherosclerosis processes. MDPI 2020-02-12 /pmc/articles/PMC7072151/ /pubmed/32059493 http://dx.doi.org/10.3390/cells9020423 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alexandru, Nicoleta
Andrei, Eugen
Safciuc, Florentina
Dragan, Emanuel
Balahura, Ana Maria
Badila, Elisabeta
Georgescu, Adriana
Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title_full Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title_fullStr Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title_full_unstemmed Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title_short Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defends Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells
title_sort intravenous administration of allogenic cell-derived microvesicles of healthy origins defends against atherosclerotic cardiovascular disease development by a direct action on endothelial progenitor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072151/
https://www.ncbi.nlm.nih.gov/pubmed/32059493
http://dx.doi.org/10.3390/cells9020423
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