Navigation Links
Testing antioxidant drugs is transparent

A study using genetically modified zebrafish to visualize early events involved in development of human atherosclerosis describes an efficient model one that the researchers say offers many applications for testing the potential effectiveness of new antioxidant 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 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.

An international team of researchers led by Yury Miller, MD, PhD, of the UCSD Department of Medicine, working with colleagues in Australia, developed an approach to see literally the accumulation of oxidized LDL in genetically modified zebrafish 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 a gene encoding an antibody that recognizes oxidized LDL, conjugated with green fluorescent protein (GFP), into the zebrafish genome. The antibody, called IK17, was originally cloned from a patient with severe coronary heart disease by the group of scientists led by Joseph L. Witztum, MD, and Sotirios Tsimikas, MD, also of the UCSD Department of Medicine.

The new gene was silent in zebrafish until their tank water was warmed to 99F (37C.) After one hour of this "heat shock," IK17-GFP was produced and eventually bound to its target oxidized LDL in the vascular wall. The green glow of GFP was clearly seen in tiny, live zebrafish under microscope. It was then put back into the fish tank until next picture-taking session.

"Using this technique, we were able to measure the time course of oxidized lipid accumulation in the vascular wall and visualize the effects of treatment with an antioxidant drug, and saw that it reversed the accumulation of oxidized LDL," said the paper's first author Longhou Fang, PhD. "The same therapeutic effect was achieved by switching the zebrafish back to a diet low in cholesterol. We saw the results in just 10 days working with the zebrafish model. A similar experiment in mice took 6 months to complete."

"I see this cholesterol-fed, transgenic zebrafish model as a novel way to study early vascular lipid accumulation and lipoprotein oxidation, the processes that lead to heart disease in humans," said Miller. "Since it is relatively easy and cost-effective to establish and maintain new transgenic zebrafish lines, this offers an in-vivo test for new antioxidants and other drug candidates that could affect development of human atherosclerosis."


Contact: Debra Kain
University of California - San Diego

Related medicine news :

1. New testing method hints at garlics cancer-fighting potential
2. Twenty-Five Years of HIV Blood Testing Helped to Positively Transform Global Health Crisis
3. Christine P. Carrington, President of NurseTesting Creative Solutions, Inducted into Cambridge Who's Who
4. New Allergy Testing Available for Patients Allergic to Penicillin: Determining the Presence of Penicillin Allergy is Essential to Patient Care
5. Breast Cancer Patients Often Confused by Genomic Testing
6. Study Results Validate Shape-HF as Simplified, Portable Cardiopulmonary Exercise Testing System
7. San Francisco AIDS Foundation Introduces HIV Testing to Sixth Street
8. Phybridge Inc. Joins the Cisco Developer Network and Completes Cisco Interoperability Verification Testing
9. UAB testing software program to improve safety among older drivers
10. Study Published by Circulation Heart Failure Reinforces Science Behind Shape-HF Cardiopulmonary Exercise Testing Device
11. Pilot Testing Phase Ends; Expansion Of Sales Force Begins
Post Your Comments:
Related Image:
Testing antioxidant drugs is transparent
(Date:11/25/2015)... ... November 25, 2015 , ... Wimbledon ... programs, launches new Wimbledon Athletics Facebook page to educate the public, ... unsuspected cardiac abnormalities. About 2,000 people under the age of 25 die from ...
(Date:11/25/2015)... ... 25, 2015 , ... Smiles by Stevens is pleased to announce ... wrinkling. While many patients are aware of the benefits of Botox® in the treatment ... those suffering with discomfort, soreness, and pain as a result of Jaw Tension, TMJ ...
(Date:11/25/2015)... , ... November 25, 2015 , ... ... decades of music, friendships, and learning in its 65th Anniversary Brillianteen Revue, scheduled ... 5-6. , For 65 years, Brillianteen has been a treasured tradition ...
(Date:11/25/2015)... D.C. (PRWEB) , ... November 25, 2015 , ... Today, ... fatalities on our nation’s roadways has dropped below 10,000 for the first time since ... 10,076 in 2013. , According to data released by the National Highway Traffic Safety ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... I found that regular bras were incredibly uncomfortable," said an inventor from Bronx, ... bra." , She developed the patent-pending RECOVERY BRA for added comfort and support. ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... 2015  Thanks to a donor with a personal ... Center,s Sister Diane Grassilli Center for Women,s Health now ... San Francisco . Fred ... with a gift of $617,320 that allowed the Center ... Tomosynthesis and Whole Breast Ultrasound. Tomosynthesis, three-dimensional (3-D) mammography ...
(Date:11/24/2015)... 24, 2015 /PRNewswire/ - ESSA Pharma Inc. ("ESSA" or ... today that the first patient has been enrolled in ... treatment for metastatic castration-resistant prostate cancer ("mCRPC"). ... --> the United States ... 1/2 clinical trial, ESSA intends to demonstrate the safety, ...
(Date:11/24/2015)... PUNE, India , November 24, 2015 ... new market research report "Spine Biologics Market by Product Type ... Type (Anterior Cervical Discectomy and Fusion, Posterior Lumbar Interbody Fusion), ... by MarketsandMarkets, the global market was valued at $1.90 Billion ... 2020, at a CAGR of 4.4% during the forecast period ...
Breaking Medicine Technology: