doi: 10.1161/CIRCRESAHA.107.157404
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© 2007 American Heart Association, Inc.
Editorials |
Old Drug, New Tricks
The Unexpected Effect of Doxazosin on High-Density Lipoprotein
From the National Institutes of Health, National Heart, Lung, and Blood Institute, Vascular Medicine Branch, Lipoprotein Metabolism Section.
Correspondence to Alan T. Remaley, National Institutes of Health, 10 Center Dr., Bldg. 10/Rm. 2C-433, Bethesda, MD 20892. E-mail aremaley@nih.gov
See related article, pages 156–165
Key Words: cholesterol • atherosclerosis • HDL • doxazosin • ABCA1
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Ironically, even though there are currently only a few drugs to specifically treat low high-density lipoprotein (HDL), numerous drugs have been observed to inadvertently alter HDL levels.1 This has been particularly noted for some antihypertensive drugs. Because they are used long-term, any positive or negative effect of antihypertensive drugs on lipids and lipoproteins can significantly impact on their effectiveness in preventing cardiovascular disease. Recently, advances in our understanding of HDL metabolism have helped us to unravel the mechanism of action of these and other drugs that unexpectedly alter HDL levels. This work has largely been led by the laboratory of Shinji Yokoyama and colleagues, who have previously identified the mechanism of action of three drugs on HDL metabolism. Probucol, which has been used to treat patients at risk for cardiovascular disease, is an antioxidant and lowers LDL, but it also lowers HDL. Probucol is now known to decrease HDL by inhibiting the activity of the ABCA1 transporter,2 a key protein involved in reverse cholesterol transport pathway and in HDL biogenesis.3 Verapamil, a calcium channel blocker, which can be used as antihypertensive and antiarrhythmic agent, and fenofibrate, a lipid-lowering drug, both raise HDL by increasing the gene expression of the ABCA1 transporter.4,5 In this issue of Circulation Research,6 Iwamoto et al describe the mechanism of action of a fourth agent that unexpectedly alters HDL, namely the antihypertensive agent doxazosin. The results of this study raise the possibility of a new strategy for developing drugs to increase HDL.
Doxazosin (Cardura) is
Related Article:
: Doxazosin Inhibits Activator Protein 2 and Increases High-Density Lipoprotein Biogenesis Independent of 1-Adrenoceptor Blockade
Circ. Res. 2007 101: 156-165.