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Breakthrough Promised In Detecting Atherosclerosis

OHSU researchers demonstrate a technique that can spot the ‘stealth’ disease long before it becomes clinically evident and pave the way for therapies that could keep it from progressing.

A study led by a team of researchers at Oregon Health & Science University has demonstrated for the first time that molecular imaging with contrast-enhanced ultrasound and targeted microbubbles is effective in detecting at a very early stage inflammatory processes that lead to atherosclerosis.

If the technique, which was tested on animal models in the study, proves viable in humans, it could pave the way for therapies that could prevent the condition from progressing and bringing on coronary heart disease and stroke, two of the nation's most lethal diseases. Such therapies could be applied at the onset of inflammation years before present screening methods would detect evidence of the stealthily progressive disease.

The researchers, led by Jonathan R. Lindner, M.D., professor of medicine in the cardiovascular division of the OHSU School of Medicine, learned in the study that a vascular adhesion molecule known as VCAM-1, which shows up on the walls of blood vessels at the onset of inflammation and plays an important role in the early development of atherosclerotic plaque, could be successfully highlighted in ultrasound images by injecting lipid microbubbles into the blood which are tipped with antibodies that cause the bubbles to "stick" to the VCAM-1 molecules.

The research team described their study in Circulation, a peer-reviewed journal of the American Heart Association.

Atherosclerosis is the hardening and narrowing of the arteries and is a disease that may start in childhood and progress over many years without producing any clinical symptoms. It leads to the slow buildup of plaque on the inside walls of arteries. The plaque – which is made up of fat, cholesterol, calcium and other substances –eventually may restrict the flow of blood. It can also break apart, causing a blood clot that can result in a heart attack, a stroke or other serious complications. Coronary heart disease and strokes are the number-one and number-three causes of death in the United States, according to the most recent data from the National Heart Lung and Blood Institute of the National Institutes of Health (NIH).

"Since inflammation participates in plaque initiation and progression, a method capable of imaging the extent of vascular inflammation could provide powerful predictive information on future risk for disease progression," said Lindner and his colleagues in the journal article.

"VCAM-1 shows up even before other changes occur in the blood vessels so it's there before there is any plaque and we know it's an important part of the mechanism by which atherosclerosis starts," said Beat A. Kaufmann, M.D., an OHSU post-doctorate fellow in cardiology who was one of the key investigators in the study. He presented the findings at the recent annual meeting of the American Society of Echocardiography (ASE), where he was awarded the ASE's prestigious 2007 Arthur E. Weyman Young Investigator's Award for his work on the study.

"There might be other targets that are better than VCAM-1, and we are looking at that. There are other molecules that also are involved in the inflammation of the artery walls in atherosclerosis. But we do know that about 40 percent of the adult U.S. population has a 6 percent to 20 percent chance of developing coronary heart disease within a decade as a result of atherosclerosis. A cost-effective method like ultrasound for detecting vascular inflammation is critical, given the large number of people at risk, if new therapies aimed at inhibiting vascular inflammation are to be initiated."

The OHSU research team, besides Lindner and Kaufmann, included Aris Xie, M.S., a senior research assistant in the cardiology division. Also participating in the study were Ian J. Sarembock, M.D.; Christopher Davis, M.D.; and John M. Sanders, B.S., all of the University of Virginia. Funding support for the research was provided by the National Heart Lung Blood Institute of NIH.

Lindner serves on the Scientific Advisory Board for Visual Sonics, manufacturer of the imaging equipment used in this research. The potential conflict of interest has been reviewed and managed by OHSU.


About Oregon Health & Science University

As a leader in research, OHSU earned $307million in research funding in fiscal year 2007. OHSU serves as a catalyst for the region's bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every 2.7 days, with more than 3,500 research projects currently under way. OHSU disclosed 132 inventions in 2007 alone, and OHSU research has resulted in 33 startup companies since 2000, most of which are based in Oregon.

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