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Updated: Jun 2, 2026

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

Atheroprotective reverse cholesterol transport pathway is defective in familial hypercholesterolemia

Natacha Bellanger1, Alexina Orsoni, Zélie Julia

  • 1Institut National de la Santé et de la Recherche Médicale, UMRS 939, Hôpital de la Pitié, Paris, France.

Arteriosclerosis, Thrombosis, and Vascular Biology
|April 30, 2011
PubMed

Insights

Familial hypercholesterolemia (FH) impairs reverse cholesterol transport, reducing high-density lipoprotein (HDL) function in cholesterol removal and increasing atherosclerosis risk.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Atherosclerosis Pathogenesis

Background:

  • Low high-density lipoprotein (HDL) cholesterol is common in familial hypercholesterolemia (FH).
  • Functional alterations in HDL particles may impair reverse cholesterol transport (RCT) in FH.
  • Understanding HDL functionality in FH is crucial for assessing atherogenicity.

Purpose of the Study:

  • To investigate the functional capacity of HDL particles in familial hypercholesterolemia.
  • To evaluate key steps of reverse cholesterol transport in FH patients compared to controls.
  • To correlate HDL function with markers of atherosclerosis.

Main Methods:

  • Assessed cellular free cholesterol efflux mediated by HDL particles.
  • Measured cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters (CE) from HDL.
  • Evaluated hepatic uptake of HDL-CE in FH patients (n=12) and controls (n=12).

Main Results:

  • FH-derived HDL2 particles showed reduced cholesterol efflux via SR-BI and ABCG1 pathways.
  • Lower HDL efflux capacity correlated inversely with carotid intima-media thickness.
  • Elevated CETP-mediated CE transfer and reduced hepatic CE delivery by HDL were observed in FH.

Conclusions:

  • Reverse cholesterol transport is defective in familial hypercholesterolemia.
  • Impaired cholesterol efflux and altered CE transfer contribute to FH atherogenicity.
  • These findings highlight the role of dysfunctional HDL in FH pathogenesis.
Abstract

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