Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transparent zebrafish a must-see model for atherosclerosis

06.03.2009
We usually think of fish as a "heart-healthy" food. Now fish are helping researchers better understand how heart disease develops in studies that could lead to new drugs to slow disease and prevent heart attacks.

Scientists at the University of California, San Diego School of Medicine have done to laboratory zebrafish exactly what many people still do to themselves – added excess cholesterol to their diet. Because young zebrafish are transparent, researchers were able to see – literally – the development of plaques in the zebrafish blood vessels.

The study led by Yury I. Miller, MD, PhD, associate professor of medicine at UC San Diego School of Medicine will be published online March 5th in advance of print in the April issue of Circulation Research, published by the American Heart Association.

"The use of this transparent zebrafish model is a promising method to screen for new drugs and cardiovascular imaging agents," said Miller.

Atherosclerosis is a process of thickening and hardening of the artery walls as a result of fat deposits and inflammation. Risk factors for atherosclerosis include high levels of "bad" cholesterol, high blood pressure (or hypertension), smoking, diabetes and a family history of the disease – all of which can lead to heart attack or stroke.

Extreme hyperlipidemia, or the presence of excess fat and cholesterol molecules in the bloodstream, has been induced in mice and rabbits in the past, but microscopic examination of plaque build-up was only possible post-mortem.

Miller and colleagues fed a high-cholesterol diet (HCD) to zebrafish, supplementing the HCD with a red fluorescent lipid. They also used fish with endothelial cells – the thin layer of cells that line the interior surface of blood vessels – that were tagged with green fluorescent protein. Fish macrophages were tagged with red fluorescent protein, illuminating these immune cells which regulate chronic inflammation and indicate the development of atherosclerosis.

"Because zebrafish are transparent for the first 30 days of life, we can see in the living fish that the blood vessels glow green, while the fat deposits in vascular plaques are red," said Miller. He added that, interestingly, the zebrafish on a high-cholesterol diet did grow little fat fish stomachs.

The scientists used confocal microscopy, able to detect the fluorescent cells, in order to monitor vascular lipid accumulation and view the thickening of the endothelial lining in the living zebrafish. In other experiments, zebrafish in which the macrophages expressed red fluorescent protein were given HCD. This resulted in the pathologic accumulation of fluorescent macrophages along the endothelial cells of the vascular wall, as happens in human atherosclerotic plaques.

To explore the potential of zebrafish for atherosclerosis-related drug screening, the researchers administered the drug ezetimibe by adding it to the fish tank water. Ezetimibe is a medication marketed as Zetia, used to lower plasma cholesterol levels by lowering cholesterol absorption in the intestine. After treating the HCD-fed zebrafish with ezetimibe, the scientists were able to literally see that the drug significantly diminished the thickening of the vascular wall and improved its barrier function.

"Many researchers and clinicians agree that the treatment of atherosclerosis must begin at the earliest possible stage – the fatty streak," said Miller. "By feeding HCD to zebrafish, we were able to reproduce many of the processes involved in early atherogenesis. Our results suggest that this new model is suitable for studying inflammatory processes that occur in the early development of the disease, by looking at the function of vascular cells and lipid deposits in a live animal."

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>