Old drug, new tricks: the unexpected effect of doxazosin on high-density lipoprotein.

摘要

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. 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, a key protein involved in reverse cholesterol transport pathway and in HDL biogenesis.