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 Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>