Editors' ChoiceCardiovascular Disease

Giving Statins a Run for Their Money?

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Science Translational Medicine  07 Mar 2012:
Vol. 4, Issue 124, pp. 124ec43
DOI: 10.1126/scitranslmed.3003949

Although organizations such as the American Heart Association advise us to limit our intake of saturated fats and cholesterol, many people do not. High cholesterol in the blood stream increases the risk of atherosclerosis, a hardening of the arteries caused by the buildup of plaque, which leads to heart attacks and strokes. Statins, which inhibit a cholesterol-producing enzyme, are currently the drugs of choice for lowering cholesterol when diet and exercise have failed, but these drugs are associated with uncomfortable side effects. Serotonin has been shown to be important for regulating cardiovascular function; its concentration in the blood is increased in conditions such as heart attacks, strokes, and high blood pressure. Thus, blocking serotonin receptors seems to be a logical approach for the prevention and treatment of cardiovascular diseases.

Xu et al. investigated the ability of a serotonin receptor antagonist called sarpogrelate (SP) to decrease blood lipid levels, oxidative stress, and blood and plasma viscosity (which increase if blood lipid levels increase) in a rabbit model. Twenty-nine adult male rabbits were divided into four groups, which were fed either normal or high-cholesterol diets with or without added SP for 90 days. As expected, as compared with those fed a normal diet, rabbits fed the high-cholesterol diet had higher levels of plasma cholesterol, triglycerides (which are associated with atherosclerosis), and malondialdehyde (a marker of oxidative stress); higher blood and plasma viscosity; and increased atherosclerotic plaque formation. When such rabbits also received SP, all of these changes were prevented or significantly reduced. Furthermore, SP treatment protected against damage to endothelial cells that line the blood vessels and decreased the number of foam cells, which form fatty streaks in arterial plaques. SP had no significant effect on lipid, malondialdehyde, or blood viscosity levels in rabbits fed the normal diet.

This is the first study to show a lipid- and viscosity-lowering effect of SP directly, suggesting a new mechanism for the prevention and treatment of atherosclerosis by SP that involves the prevention of endothelial cell damage, reduction of atherosclerotic plaque size, and reduction in the formation of foam cells. SP might give statins a run for their money with fewer side effects.

Y. J. Xu et al., Suppression of high lipid diet induced atherosclerosis by sarpogrelate. J. Cell Mol. Med. 20 February 2012 (10.1111/j.1582-4934.2012.01554.x). [Abstract]

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