Published Online
on September 2, 2008

A more recent version of this article appeared on September 16, 2008

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Submitted on February 4, 2008
Accepted on July 11, 2008

Combined Statin and Niacin Therapy Remodels the High-Density Lipoprotein Proteome

Pattie S. Green PhD^*, Tomas Vaisar PhD, Subramaniam Pennathur MD, J. Jacob Kulstad PhD, Andrew B. Moore BS, Santica Marcovina PhD, John Brunzell MD, Robert H. Knopp MD, Xue-Qiao Zhao MD, and Jay W. Heinecke MD

From the Department of Medicine, University of Washington, Seattle.

^* To whom correspondence should be addressed. E-mail: psgreen{at}u.washington.edu.

Background—Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL₃ of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL. We hypothesized that an intervention that increases HDL levels—combined statin and niacin therapy—might reverse these changes.

Methods and Results—HDL₃ isolated from 6 coronary artery disease subjects before and 1 year after combination therapy was analyzed by liquid chromatography–Fourier transform–mass spectrometry. Alterations in protein composition were detected by spectral counting and confirmed with extracted ion chromatograms. We found that combination therapy decreased the abundance of apolipoprotein E in HDL₃ while increasing the abundance of other macrophage proteins implicated in reverse cholesterol transport. Treatment-induced decreases in apolipoprotein E levels of HDL₃ were validated biochemically in a second group of 18 coronary artery disease subjects. Interestingly, the changes in HDL₃ proteome with niacin/statin treatment resulted in a protein composition that more closely resembled that of HDL₃ in healthy control subjects.

Conclusions—Combined statin and niacin therapy partially reverses the changes in the protein composition seen in HDL₃ in coronary artery disease subjects. Our observations raise the possibility that quantifying the HDL proteome could provide insights into the therapeutic efficacy of antiatherosclerotic interventions.

Key words: arteriosclerosis • cardiovascular diseases • drugs • inflammation • lipoproteins

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Circulation 2008 118: 1217-1218. [Extract] [Full Text]

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