A fluorescent test for antioxidant drugs

November 25, 2011

A zebrafish model of atherosclerosis (credit: UC San Diego School of Medicine)

A study by UC San Diego School of Medicine, with colleagues in Australia, to visualize accumulation of oxidized LDL in genetically modified zebrafish could lead to a rapid test for the potential effectiveness of new antioxidant and dietary therapies for human atherosclerosis.

Atherosclerosis is a process of lipid deposition and inflammation in the artery walls. Low-density lipoprotein (LDL) that carries “bad” cholesterol in blood is easily oxidized, and oxidized LDL promotes inflammatory responses by vascular cells. Inflamed atherosclerotic plaque can often rupture; this results in a blood clot, obstruction of blood flow to the heart or brain, and heart attack or stroke.

The zebrafish were fed a diet high in cholesterol. Because young zebrafish are transparent, the researchers were able to study vascular lipid accumulation, lipid oxidation, and uptake of oxidized LDL by macrophages, all in live animals.

To be able to see oxidized LDL, the researchers inserted into the zebrafish genome a gene that codes for an antibody that recognizes oxidized LDL, conjugated with green fluorescent protein (GFP).

Ref.: Longhou Fang et al., In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish, Journal of Clinical Investigation, 2011 [doi:10.1172/JCI57755]