Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

Author:

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

Abstract

AbstractHypercholesterolemia (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.

Funder

Magyarország Kormánya

Richter Gedeon Talentum Alapítvány,Hungary

Science Foundation Ireland

Nemzeti Kutatási és Technológiai Hivatal

Semmelweis University

Publisher

Springer Science and Business Media LLC

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