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Two Chinese Scientists Played in Key Roles in the Study to Find New Approach to Unclogging Arteries www.famouschinese.com

WASHINGTON, Aug 16 (Reuters) - U.S. researchers said they had found a key mechanism involved when cholesterol clogs arteries, and said it may open up a whole new way to treat and prevent heart attacks and stroke. Drugs first developed 40 years ago, and then abandoned, could help prevent clots from breaking off and clogging the artery, they report. When people have too much cholesterol in their blood, immune cells called macrophages seize fatty particles and try to drag them out through the walls of the artery. But they are too big, get stuck and eventually the macrophages die. These plugs of dead cells are what causes atherosclerosis -- the hardening and clogging of the arteries. In two papers published in the Proceedings of the National Academy of Sciences and Nature Cell Biology this week, Dr. Ira Tabas of Columbia University in New York and colleagues, Dr. Bo Feng and Dr. Dajun Zhang, showed they had found the mechanism that kills the cells, and a drug that may stop the process. Dr. Feng and Dr. Zhang, both came from Tongji Medical College of Huazhong Univeristy of Science and Technology. They have been working on this field for many years. "In order to get atherosclerosis, you need two things going on -- you need high levels of LDL (low-density lipoprotein or 'bad' cholesterol) in the blood and you need events going in the arterial wall," Tabas said in a telephone interview. "Statins are utterly fantastic at lowering LDL," he said. But they only lower the risk of stroke or heart attack by about 30 percent. Tabas believes a drug that could stop the macrophages from dying and clogging up the arteries in the first place would work in tandem with statins and similar drugs to prevent heart disease. MESSING UP THE PROTEINS When a macrophage gobbles up a piece of cholesterol, it is moved to an organelle inside the cell called the endoplasmic reticulum. This is the machine responsible for making the cell's proteins, and making proteins is what cells must do to survive and function. "This causes the endoplasmic reticulum to function poorly," Tabas said. "That, in turn, sets up a death program in the cell." It turns out there is a drug that stops the cholesterol from getting into the cells in the first place. "In the late 1950s and early 1960s, people learned one enzyme, if blocked, could block cholesterol biosynthesis," Tabas said. But drugs that blocked the enzyme only worked at high doses and caused side-effects in animals such as cataracts, so they were never developed. Tabas found that extremely low doses the drugs, specifically one called U18666A, very specifically prevents cholesterol from getting into the endoplasmic reticulum. This could offer a route to treating heart disease with few side effects. The more specific a drug's action, and the lower the dose needed, the less likely it is to cause side effects. Pfizer (NYSE:PFE - News) now owns the rights to U18666A, but Tabas's group has patented the application and is working with Richmond, California-based Berlex Biosciences to develop a drug that takes similar action. The study also raises the question of whether some people may genetically resist heart disease. A genetic defect also prevents cholesterol from getting into cells. In children with two copies of the "bad" gene it causes a deadly nerve condition called Niemann-Pick C disease. But Tabas wonders whether people with just one copy of the "bad" gene might be protected from heart disease. He is starting a study with parents of Niemann-Pick C patients -- who may have just one mutated copy of the gene -- to see if they have a lower risk of clogged arteries. SOURCE: Feng B, Zhang D, Kuriakose G, Devlin CM, Kockx M, Tabas I. Niemann-Pick C heterozygosity confers resistance to lesional necrosis and macrophage apoptosis in murine atherosclerosis. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10423-8. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas I. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol. 2003 Sep;5(9):781-92.