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Cholesterol Efflux Assay
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Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles

Csenger Kovácsházi1, Szabolcs Hambalkó1, Nabil V Sayour1

  • 1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.

Scientific Reports
|May 26, 2024
PubMed

Insights

High cholesterol (hypercholesterolemia) alters circulating and cardiomyocyte extracellular vesicles (EVs). These changes in EVs may contribute to heart problems caused by high cholesterol.

Area of Science:

  • Cardiovascular Biology
  • Metabolomics
  • Extracellular Vesicle Research

Background:

  • Hypercholesterolemia (HC) is a major risk factor for cardiovascular diseases, but its precise mechanisms remain unclear.
  • Extracellular vesicles (EVs) play a role in disease pathogenesis, including cardiovascular conditions.

Purpose of the Study:

  • To investigate the impact of HC on the metabolomic profile of circulating EVs.
  • To analyze the proteomic and functional characteristics of cardiomyocyte (CM)-derived EVs in HC.

Main Methods:

  • Circulating EVs were isolated from rats fed a high-cholesterol diet using Vezics technology.
  • Cardiomyocyte-derived EVs were analyzed after treating AC16 human CMs with a hypercholesterolemia supplement.
  • EVs' biophysical properties, protein composition, and effects on monocyte activation were assessed.

Main Results:

  • HC diet altered phosphatidylcholine levels in circulating EVs.
  • HC significantly increased EV secretion from CMs and modified their proteome, including proteins involved in tissue remodeling.
  • CM-derived EVs did not induce monocyte activation.

Conclusions:

  • Hypercholesterolemia significantly impacts the metabolome of circulating EVs and dysregulates CM-derived EVs.
  • These EV alterations may contribute to cardiac dysfunction in HC.
  • Further research is needed to fully elucidate the role of EVs in HC-induced cardiovascular derangements.

Keywords:
DyslipidemiaExosomeInflammationMetabolomicsObesityProteomics

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