Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps scientists link ozone to atherosclerosis

07.11.2003


Detection of toxic ’atheronal’ molecules may lead to new diagnostics

A team of investigators led by The Scripps Research Institute (TSRI) President Richard A. Lerner, M.D., and TSRI Associate Professor Paul Wentworth, Jr., Ph.D., are reporting evidence for the production of ozone in fatty atherosclerotic plaques taken from diseased arteries.

Lerner is Lita Annenberg Hazen Professor of Immunochemistry and holds the Cecil H. and Ida M. Green Chair in Chemistry at TSRI. He is also one of several scientists on the team who are members of The Skaggs Institute for Chemical Biology at TSRI.



Lerner, Wentworth, and their colleagues have been looking at the production of ozone molecules within the human body for the last year and a half, ever since they made the completely unexpected discovery that human antibodies generate a product with the chemical signature of ozone. Ozone is a highly reactive molecule that has never before been considered part of biology.

So if antibodies produce ozone in the human body, the TSRI scientists asked, what is the ozone doing there? Their report, out in this week’s issue of the journal Science, details what they found.

In their report, Lerner, Wentworth, and their colleagues describe how ozone can trigger pathological changes in other molecules in the body, like cholesterol, which ozone breaks down to produce toxic compounds. The scientists describe two such compounds, which they call the "atheronals." These atheronals were found in atherosclerotic plaques that were surgically removed from patients with atherosclerosis.

The scientists suggest these newly identified products are critical to the pathogenesis of atherosclerosis because they are toxic to white blood cells, smooth muscle cells, and cells from the arterial walls--all the major types of cells in and around atherosclerotic plaques. Furthermore, they suggest that atheronals and similar products of ozonolysis may contribute to a number of other diseases, such as lupus, multiple sclerosis, and rheumatoid arthritis.

"Ozone is damaging, and it is really a problem that we are going to have to think about in the next few years," says Wentworth. "There may be a whole slew of molecules that ozone generates that we have never thought about before."

Finally, Lerner, Wentworth, and their colleagues detail how one of the atheronals was found in the blood of patients who have late-stage atherosclerosis, but not in healthy individuals. This suggests that the presence of atheronals may be a good indicator of late-stage arterial inflammation--perhaps the basis for a diagnostic test for atherosclerosis.

Currently, physicians use other risk factors to identify a patient’s risk: elevated cholesterol, hypertension, diabetes, smoking, obesity and a family history of vascular disease at an age less than 55. These indicators are not always reliable, and there is a substantial fraction of patients who develop atherosclerosis without displaying these risk factors.

Sensitive diagnostic markers that would allow early identification of patients at risk of life-threatening atherosclerosis would be a boon to preventative medicine.

Atherosclerosis and Ozone

Atherosclerosis is a common vascular disease that increases the risk of heart attacks and strokes. In fact, heart disease is the most common cause of death in the United States. The Centers for Disease Control and Prevention statistics for 2000 list 878,471 deaths from heart disease and stroke, followed by 553,091 for cancer.

The name of the disease comes from the Greek athero (which means gruel or paste) and sclerosis (which means hardness). And, as the name implies, it is a disease that is characterized by a hardening of the arteries over time due to the buildup of hard plaques--fibrous tissue, calcium, fat, cholesterol, proteins, cells, and other materials--on the inner "endothelial" walls of an artery. These plaques feel something like cartilage to the touch, which explains why atherosclerosis is commonly called hardening of the arteries.

Over the last few years, evidence has been accumulating that the process of atherosclerosis has a significant inflammatory component. Given this evidence, Lerner, Wentworth and their colleagues thought they would look at tissue involved in the disease for evidence of ozone.

Ozone is a particularly reactive form of oxygen that exists naturally as a trace gas in the atmosphere, constituting on average fewer than one part per million air molecules. The gas plays a crucial role in protecting life on earth from damaging solar radiation by concentrating in the upper reaches of Earth’s stratosphere--about 25 kilometers above the surface--and absorbing ultraviolet radiation. Ozone is also a familiar component of air in industrial and urban settings where the highly reactive gas is a hazardous component of smog in the summer months.

A few years ago, Lerner and Wentworth made the completely unexpected discovery that ozone is involved in human biology.

Lerner and Wentworth realized that atherosclerotic plaques have all the ingredients needed to make ozone. They contain white blood cells, which have the ability to generate the singlet oxygen that the antibodies need to produce ozone--and plenty of antibodies passing by in the blood stream.

Ozone Present in Atherosclerotic Plaques

Last year, Lerner and Wentworth approached Giacomo DeLaria, M.D., who is a vascular surgeon at nearby Scripps Clinic, and asked if they could obtain samples of carotid atherosclerotic plaques. DeLaria provided a sample of plaque material from a patient who recently underwent an endarterectomy, generously enabling Wentworth, Lerner, and their colleagues to perform their studies. Endarterectomies are common surgical procedures to remove plaques from the inner walls of atherosclerotic arteries.

"These are specimens we normally just inspect and throw away," says DeLaria, who is a coauthor of the study. "Within themselves, they have no diagnostic value, and they don’t change what we do after the procedure."

Wentworth and Lerner tested this sample, and the results proved promising. They found some abnormalities that could be associated with the presence of ozone in these plaques. But they wanted to be sure. So DeLaria and his fellow vascular surgeon Ralph Dilley, M.D., provided several more samples.

When Lerner, Wentworth, and their colleagues studied the atherosclerotic plaque samples, they found the evidence they were looking for. The atheronals--signature products that were produced when the highly reactive ozone mixed with cholesterol--were evident in the plaques. This suggests that ozone production occurred as these plaques were being formed.

Jason Bardi | EurekAlert!
Further information:
http://www.sciencemag.org

More articles from Health and Medicine:

nachricht Scientists discover the basics of how pressure-sensing Piezo proteins work
22.08.2019 | Weill Cornell Medicine

nachricht Protein-transport discovery may help define new strategies for treating eye disease
22.08.2019 | Scripps Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Hamburg and Kiel researchers observe spontaneous occurrence of skyrmions in atomically thin cobalt films

Since their experimental discovery, magnetic skyrmions - tiny magnetic knots - have moved into the focus of research. Scientists from Hamburg and Kiel have now been able to show that individual magnetic skyrmions with a diameter of only a few nanometres can be stabilised in magnetic metal films even without an external magnetic field. They report on their discovery in the journal Nature Communications.

The existence of magnetic skyrmions as particle-like objects was predicted 30 years ago by theoretical physicists, but could only be proven experimentally in...

Im Focus: Physicists create world's smallest engine

Theoretical physicists at Trinity College Dublin are among an international collaboration that has built the world's smallest engine - which, as a single calcium ion, is approximately ten billion times smaller than a car engine.

Work performed by Professor John Goold's QuSys group in Trinity's School of Physics describes the science behind this tiny motor.

Im Focus: Quantum computers to become portable

Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.

Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...

Im Focus: Towards an 'orrery' for quantum gauge theory

Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics

The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Making small intestine endoscopy faster with a pill-sized high-tech camera

23.08.2019 | Medical Engineering

More reliable operation offshore wind farms

23.08.2019 | Power and Electrical Engineering

Tracing the evolution of vision

23.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>