Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myoc...

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Published in:	Scientific reports Vol. 14; no. 1; p. 12016
Main Authors:	Kovácsházi, Csenger, Hambalkó, Szabolcs, Sayour, Nabil V., Gergely, Tamás G., Brenner, Gábor B., Pelyhe, Csilla, Kapui, Dóra, Weber, Bennet Y., Hültenschmidt, Alexander L., Pállinger, Éva, Buzás, Edit I., Zolcsák, Ádám, Kiss, Bálint, Bozó, Tamás, Csányi, Csilla, Kósa, Nikolett, Kellermayer, Miklós, Farkas, Róbert, Karvaly, Gellért B., Wynne, Kieran, Matallanas, David, Ferdinandy, Péter, Giricz, Zoltán
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 26-05-2024 Nature Publishing Group Nature Portfolio
Subjects:	631/250 631/250/256 631/337 631/337/475 631/57 631/57/2270 631/61 631/61/320 631/61/475 631/80 631/80/2023 631/80/304 631/80/313 631/80/86/2365 631/80/86/2366 631/80/86/820 692/4019 692/4019/592 692/4019/592/75 692/4019/592/75/2099 692/699 692/699/317 692/699/75 692/699/75/2099 Animals Cardiomyocytes Cardiovascular diseases Cell activation Cell culture Cholesterol Dyslipidemia Exosome Extracellular vesicles Extracellular Vesicles - metabolism Humanities and Social Sciences Humans Hypercholesterolemia Hypercholesterolemia - blood Hypercholesterolemia - metabolism Hypercholesterolemia - pathology Inflammation Male Metabolomics Monocytes Monocytes - metabolism multidisciplinary Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Obesity Protein composition Proteomes Proteomics Rats Rats, Wistar Science Science (multidisciplinary) Obesity Metabolomics Inflammation Exosome Dyslipidemia Proteomics
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Summary:	Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-62689-6