(Open access funding provided by Semmelweis University)
(VEKOP-2.3.3-15-2017-00016)
(K139105)
(NVKP-16-1-2016-0017 National Heart Program) Támogató: NKFIH
(TKP2021-EGA-23) Támogató: Innovációs és Technológiai Minisztérium
(2020-4.1.1.-TKP2020)
(RRF-2.3.1-21-2022-00003)
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
(ÚNKP-23-3-II-SE-42)
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.
