Related Experiment Video

Updated: Jul 14, 2026

Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

Bone marrow-derived multidrug resistance protein ABCB4 protects against atherosclerotic lesion development in LDL

Marieke Pennings1, Reeni B Hildebrand, Dan Ye

  • 1Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. pennings@lacdr.leidenuniv.nl

Cardiovascular Research
|June 15, 2007
PubMed
Abstract

Insights

Bone marrow-derived ABCB4 limits macrophage foam cell formation, an important anti-atherosclerotic function. This study found that lacking ABCB4 in macrophages increased atherosclerotic lesion size despite lower cholesterol levels.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Atherosclerosis Research

Background:

  • ATP binding cassette (ABC)-transporter superfamily members in macrophages aid cholesterol and phospholipid efflux, protecting against atherosclerosis.
  • ABCB4 is crucial for cellular lipid efflux, as evidenced by impaired biliary lipid secretion in its absence.
  • The specific role of bone marrow-derived ABCB4 in atherosclerosis remains to be elucidated.

Purpose of the Study:

  • To investigate the function of bone marrow-derived ABCB4 in the development of atherosclerotic lesions.
  • To determine if ABCB4 deficiency in macrophages influences atherosclerotic plaque formation.

Main Methods:

  • Bone marrow transplantation was used to create LDL receptor knockout (LDLr-/-) mice lacking ABCB4 in bone marrow-derived cells.
  • Mice were fed a high-cholesterol diet to induce atherosclerotic lesion development.
  • In vitro foam cell formation assays were performed using peritoneal macrophages.

Main Results:

  • Mice lacking ABCB4 in bone marrow exhibited significantly lower serum cholesterol levels.
  • Despite reduced serum cholesterol, ABCB4 deficiency led to a 1.8-fold increase in atherosclerotic lesion size.
  • In vitro, macrophages lacking ABCB4 showed increased acetylated LDL (AcLDL) association and enhanced foam cell formation, with unaffected cholesterol efflux.

Conclusions:

  • Bone marrow-derived ABCB4 plays a significant anti-atherosclerotic role.
  • ABCB4 likely limits atherosclerotic lesion development by inhibiting macrophage foam cell formation.

More Related Videos

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice07:36

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice

Published on: September 26, 2018

Isolation and Analysis of Aortic Arch and Root Lesions in an Atherosclerotic Mouse Model07:49

Isolation and Analysis of Aortic Arch and Root Lesions in an Atherosclerotic Mouse Model

Published on: February 14, 2025

Related Concept Videos

Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...