This is important news for about 14 million people in the United States who suffer from coronary artery disease and the 1.1 million who could experience heart attacks and death, noted Artiom Petrov, Ph.D., co-author of "Resolution of Apoptosis in Atherosclerotic Plaque by Dietary Modification and Statin Therapy." Atherosclerosis is the slow, progressive buildup of deposits called plaques on the inner walls of arteries, which carry oxygen-rich blood to the heart, brain and other parts of the body. Over time, plaques--deposits of fat, cholesterol and calcium--can narrow coronary arteries, allowing less blood to flow to the heart muscle. Rupture of these plaques may result in acute (sudden) events, such as heart attack and death.
More than two-thirds of acute coronary events result from rupture of coronary plaques, said Petrov, a researcher in the division of cardiology at the University of California at Irvine. These plaques are likely to have large lipid (fat) collections, which are often associated with hemorrhages and harbor significant inflammation, said Petrov, explaining that inflamed cells often undergo apoptosis or suicidal death. An international team of researchers used the radiolabeled protein annexin A5 for the noninvasive imaging of atherosclerotic plaques in experimental rabbit models, binding it to the cell membrane surfaces of dying cells. By using a nuclear medicine procedure and exploring the role of diet modification and use of statins, which are cholesterol-lowering drugs, researchers found that "the radiotracer uptake demonstrated a significant correlation with inflammatory cell prevalence and the magnitude of cell death in plaques," said Petrov.
The study's findings "allow us to propose that stabilization of these plaques is a possibility," he said. This supports "the paradigm of prevention rather than treatment of a coronary event," said Petrov. The study "demonstrates that a decrease in apoptosis was associated with behavioral and therapeutic interventions--diet modification and use of statins--known to improve outcomes in coronary artery disease," he said. "Given that apoptosis contributes to plaque vulnerability, manipulation of apoptosis in atherosclerotic plaques may be of value in treating patients," said Petrov. "Our studies offer a proof of concept for commonly employed strategies for the primary and secondary prevention of coronary events," he added. Additional work needs to be done in developing techniques to combine morphologic and functional imaging about plaques for them to become clinically applicable, said Petrov. He noted that this experimental study is a step toward demonstrating the virtues of molecular imaging.
The investigation was performed in the research laboratories of Jagat Narula, M.D., Ph.D., professor of medicine and chief of the division of cardiology at the University of California, Irvine. Besides Petrov and Narula, authors of "Resolution of Apoptosis in Atherosclerotic Plaque by Dietary Modification and Statin Therapy" include Dagmar Hartung, M.D., School of Medicine Hannover, Hannover, Germany, and division of cardiology, University of California at Irvine; Masayoshi Sarai, M.D., Navneet Narula, M.D., and Johan Verjans, M.D., all with the division of cardiology at the University of California at Irvine; Frank Kolodgie, Ph.D., and Renu Virmani, M.D., both Cardiovascular Pathology, Gaithersburg, Md.; and Chris Reutelingsperger, Ph.D., and Leo Hofstra, M.D., Ph.D., with the University Hospital Maastricht, Maastricht, the Netherlands.
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