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Could vitamins raise levels of bad cholesterol? Animal study suggests they might

ggested that antioxidant vitamins prevented biochemical changes that made cholesterol form plaques that can block blood flow through the arteries. Although some subsequent clinical studies seemed to back up these findings, others did not.

The new study by Dr. Fisher and his colleagues provides a different perspective on antioxidants. Surprisingly, his group found that antioxidants hampered a process in the liver that prevents the production of harmful lipoproteins.

When cells are under "oxidative stress," free radicals produced by the normal conversion of polyunsaturated fatty acids to lipid peroxides bombard the cells. The scientists discovered that liver cells respond by activating a pathway that breaks down ApoB100, a critical protein component of VLDL and other harmful lipoproteins. Deprived of the ApoB, the liver cannot now produce these bad lipoproteins and their secretion into the bloodstream is reduced substantially.

In further experiments, vitamin E, a well-known antioxidant, prevented the activation of the lipoprotein-breakdown pathway in rat and mouse liver cells. Thus, the liver destroyed fewer of the bad lipoproteins.

The study also explains why polyunsaturated fatty acids, the good fatty acids found in cold water fish, are healthy for the heart. In another series of experiments, the scientists show that omega-3 and omega-6 fatty acids activated the pathway in the liver that breaks down the bad lipoproteins. Dr. Fisher's group recently described this pathway, which they dubbed PERPP for post-ER presecretory proteolysis.

The scientists also found that the polyunsaturated fatty acids increased the generation of lipid peroxidation products (these compounds produce the nasty smell of rancid fish) and stimulated the PERPP pathway. In addition to the studies with liver cells in laboratory dishes, they also demonstrated the relationship between lipid peroxidation and reduced production of
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Contact: Jennifer Berman
Jennifer.Berman@med.nyu.edu
212-404-3555
New York University Medical Center and School of Medicine
3-May-2004


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