Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Testing antioxidant drugs is transparent

22.11.2011
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:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>