Cardiology researchers at Cedars-Sinai Medical Center have found that a single injection of a harmless virus engineered to carry a beneficial, mutant gene enabled animals to manufacture their own supply of the gene’s protein product that protects against plaque buildup in blood vessels. As a result, the amount of plaque was significantly reduced, as was an immune reaction that can lead to plaque buildup and rupture, which can cause a blocked artery and heart attack or stroke. The researchers will present their findings from this and other studies at the American Heart Association Scientific Sessions 2005 Nov. 13 through 16 in Dallas. They are pursuing a variety of approaches to interrupt the complex processes leading to plaque formation and rupture, seeking new ways to treat and even prevent atherosclerosis. Apolipoprotein A-I (apo A-I) is a protein that becomes part of HDL, or “good” cholesterol. About 25 years ago, a family in northern Italy was found by Italian researchers to have a mutation in the gene responsible for making the protein. The mutant form (apo A-I Milano) appeared to protect its carriers from cardiovascular disease. In 1994, Cedars-Sinai researchers led by Prediman K. Shah, M.D., director of the Division of Cardiology and the Atherosclerosis Research Center, showed for the first time that intravenous injection of a genetically engineered form of the protein markedly reduced arterial plaque buildup in animals fed a high cholesterol diet. A series of subsequent studies in genetically engineered mice conducted in Shah’s laboratory confirmed the potent effects of apo A-I Milano protein on prevention and reversal of plaque build-up. Based on the results of Shah’s studies, a clinical trial was conducted in humans with similar results. After five weeks of once-a-week injections, apo A-I Milano significantly shrank plaque in coronary arteries. The protein appeared to actually remove bad cholesterol, even from sites on arteries where plaque had accumulated.
