Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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 99ºF (37ºC.) 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."

Additional contributors to the study are Simone R. Green, Ji Sun Baek, Sang-Hak Lee, and Elena Deer of UC San Diego Department of Medicine; and Felix Ellett and Graham J. Lieschke of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia and the Australian Regenerative Medicine Institute at Monash University.

Funding was provided by the National Institutes of Health, the UC Tobacco-Related Disease Program, the UC San Diego Clinical and Translational Institute and the Leducq Foundation.

Miller and Fang are inventors on patents and patent applications for the potential commercial use of hypercholesterolemic zebrafish, and Witztum and Tsmikas are inventors on patents and patent applications for potential commercial use of antibodies to oxidized LDL, all held by UC San Diego.

Debra Kain | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>