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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>