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Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy
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Apolipoprotein E isoforms differentially affect LCAT-dependent cholesterol esterification.

Cecilia Vitali1, Chiara Pavanello2, Marta Turri2

  • 1Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Atherosclerosis
|September 19, 2023
PubMed
Summary
This summary is machine-generated.

The apoE2 isoform significantly increases cholesterol esterification mediated by LCAT, impacting lipoprotein metabolism. This finding highlights apoE2

Keywords:
Apolipoprotein EFish-Eye diseaseHigh density lipoproteinslecithin:cholesterol acyltransferase

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Area of Science:

  • Lipid metabolism
  • Biochemistry
  • Cardiovascular research

Background:

  • Lecithin-cholesterol acyltransferase (LCAT) esterifies cholesterol in high-density lipoprotein (HDL) and apoB-lipoproteins.
  • Apolipoprotein E (apoE) isoforms (E2, E3, E4) are key activators of LCAT's β-activity.

Purpose of the Study:

  • To investigate how different apoE isoforms influence LCAT-mediated cholesterol esterification.
  • To understand the role of LCAT in apoB-containing lipoprotein metabolism.

Main Methods:

  • Evaluated plasma cholesterol esterification rate (CER) in 311 individuals with apoE2, apoE3, or apoE4.
  • Assessed CER in 28 individuals with LCAT mutations (Fish-Eye Disease).
  • Analyzed LCAT kinetics with reconstituted HDLs (rHDLs) containing each apoE isoform using Michaelis-Menten modeling.

Main Results:

  • Plasma CER was ~20% higher in apoE2 carriers vs. apoE3, and ~30% higher vs. apoE4, even after adjustments.
  • ApoE2-containing rHDLs showed lower affinity but a higher maximal esterification rate compared to apoE3 and apoE4.
  • Similar trends were observed in individuals with FED-causing mutations.

Conclusions:

  • The apoE2 isoform is associated with enhanced LCAT-mediated cholesterol esterification.
  • This suggests unique functional properties of apoE2 that influence lipid metabolism.