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Vascular lipid accumulation seen in young transparent zebrafish by 123wert sdfsf





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Vascular lipid accumulation seen in young transparent zebrafish by
Article Posted: 01/06/2013
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Vascular lipid accumulation seen in young transparent zebrafish


 
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A study using genetically modified zebrafish to visualize earlyevents involved in development of human atherosclerosis describesan efficient model - one that the researchers say offers manyapplications for testing the potential effectiveness of newantioxidant and dietary therapies. The research, led by scientists from the University of California,San Diego School of Medicine, has been published online by the Journal of Clinical Investigation , and will appear in print in the December 1 issue of the journal. Atherosclerosis is a process of lipid deposition and inflammationin the artery walls. Low-density lipoprotein (LDL) that carries"bad" cholesterol in blood is easily oxidized, and oxidized LDL promotesinflammatory responses by vascular cells.



Inflamed atheroscleroticplaque can often rupture; this results in a blood clot, obstructionof blood flow to the heart or brain, and heart attack or stroke . An international team of researchers led by Yury Miller, MD, PhD,of the UCSD Department of Medicine, working with colleagues inAustralia, developed an approach to see - literally - theaccumulation of oxidized LDL in genetically modified zebrafish feda diet high in cholesterol. Because young zebrafish aretransparent, the researchers were able to study vascular lipidaccumulation, lipid oxidation, and uptake of oxidized LDL bymacrophages - all in live animals. To be able to see oxidized LDL, the researchers inserted a geneencoding an antibody that recognizes oxidized LDL, conjugated withgreen fluorescent protein (GFP), into the zebrafish genome.



Theantibody, called IK17, was originally cloned from a patient withsevere coronary heart disease by the group of scientists led by Joseph L. Witztum, MD, andSotirios Tsimikas, MD, also of the UCSD Department of Medicine. The new gene was silent in zebrafish until their tank water waswarmed to 99 F (37 C.) After one hour of this "heat shock,"IK17-GFP was produced and eventually bound to its target - oxidizedLDL in the vascular wall. The green glow of GFP was clearly seen intiny, live zebrafish under microscope.



It was then put back intothe fish tank until next picture-taking session. "Using this technique, we were able to measure the time course ofoxidized lipid accumulation in the vascular wall and visualize theeffects of treatment with an antioxidant drug, and saw that itreversed the accumulation of oxidized LDL," said the paper's firstauthor Longhou Fang, PhD. "The same therapeutic effect was achievedby switching the zebrafish back to a diet low in cholesterol. Wesaw the results in just 10 days working with the zebrafish model. Asimilar experiment in mice took 6 months to complete." "I see this cholesterol-fed, transgenic zebrafish model as a novelway to study early vascular lipid accumulation and lipoproteinoxidation, the processes that lead to heart disease in humans," said Miller.



"Since it is relatively easy andcost-effective to establish and maintain new transgenic zebrafishlines, this offers an in-vivo test for new antioxidants and otherdrug candidates that could affect development of humanatherosclerosis." Additional References Citations.

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