Cholesterol-lowering drug might not promote healthy hearts
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Antioxidants, such as beta-carotene and Vitamin E, have been touted for their ability to protect against heart disease.
This protective effect is attributed to their ability to prevent the oxidation of bad cholesterol by free radicals - a process thought to contribute to the build-up of disease-causing fatty deposits on artery walls. But a new study, published in The Journal of Experimental Medicine, suggests that the heart-healthy effect of one antioxidant has little to do with cholesterol oxidation.
A group of researchers at the University of New South Wales in Australia, led by Roland Stocker, studied a cholesterol-lowering drug called Probucol (Lorelco) in laboratory rodents with vascular disease. Probucol reduces the risk of heart disease in humans, but is no longer prescribed in the US and Australia because of adverse side effects: a tendency to lower good cholesterol along with the bad and the potential to induce an irregular heartbeat. Probucol is still available in Canada and Europe.
In their new study, Stocker and his colleagues show that the protective effect of probucol has nothing to do with its ability to scavenge oxygen free radicals, as the free radical-busting part of the drug alone was ineffective in protecting animals against heart disease. Instead, a different part of the probucol molecule was doing the beneficial work.
In fact, contrary to widely accepted opinion, the group found no relationship between the levels of oxidized cholesterol in blood vessels and the severity of heart disease. This might help explain the disappointing results of clinical trials with other free radical-scavenging antioxidants, such as Vitamin E, which have shown no protective effect against heart disease in humans.
The protective effect of these compounds depended on the induction of a cellular enzyme called heme oxygenase-1 (HO-1). HO-1 is known to protect against atherosclerosis in animal models, although the mechanism is not completely clear. Not surprisingly, HO-1 was not induced by Vitamin E.
Drugs closely related to probucol that contain the protective part of the drug were just as protective as the original drug. If these probucol relatives - one of which is now being tested in humans - are free of side effects, they may provide a more effective alternative to current therapies.
http://www.jem.org
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