JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish

  • 0Department of Medicine, UCSD, La Jolla, California 92093, USA.
The Journal of Clinical Investigation +

|

November 23, 2011

|

November 23, 2011

Related Experiment Videos

Contact us if these videos are not relevant.

View abstract on PubMed

Summary

This summary is machine-generated.

Transgenic zebrafish expressing an antibody against oxidized LDL (malondialdehyde-modified LDL) were used to visualize and test therapies for atherosclerosis. This model efficiently evaluates antioxidant strategies for preventing vascular lipid accumulation.

Area Of Science

  • Cardiovascular Research
  • Biomedical Imaging
  • Zebrafish Models

Background

  • Oxidative modification of low-density lipoprotein (LDL) is a critical early step in atherosclerosis development.
  • Malondialdehyde (MDA)-modified LDL forms immunogenic epitopes, targeted by antibodies used in research and imaging.
  • Existing methods for studying atherosclerosis progression and therapeutic interventions can be limited.

Purpose Of The Study

  • To develop and validate a transgenic zebrafish model for studying atherosclerosis.
  • To assess the efficacy of antioxidant and dietary interventions in a live animal model.
  • To investigate the potential therapeutic role of antibodies targeting oxidized LDL.

Main Methods

  • Engineered transgenic zebrafish with temperature-inducible expression of EGFP-labeled anti-MDA-LDL antibody (IK17).
  • Utilized optically transparent zebrafish larvae for in vivo imaging studies.
  • Administered high-cholesterol diet (HCD) and assessed vascular lipid accumulation via confocal microscopy.
  • Evaluated the impact of antioxidant treatment and regression diets on antibody binding and lipid levels.

Main Results

  • HCD induced vascular lipid accumulation, visualized using a fluorescent lipid marker.
  • IK17-EGFP expression allowed real-time monitoring of MDA epitope accumulation in vascular lesions.
  • Antioxidant treatment and regression diets reduced IK17 binding, indicating decreased oxidized LDL.
  • IK17-expressing larvae inhibited MDA-LDL binding to macrophages and prevented HCD-induced lipid accumulation.

Conclusions

  • Transgenic zebrafish with conditional antibody expression provide an efficient platform for studying atherosclerosis.
  • This model is suitable for evaluating dietary and antioxidant therapeutic strategies.
  • The anti-MDA-LDL antibody (IK17) shows potential as a therapeutic agent against atherosclerosis.

Related Experiment Videos

Contact us if these videos are not relevant.

Related Concept Videos