HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: R800097-JLR200v1 50/Supplement/S167    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heinecke, J. W. Search for Related Content PubMed PubMed Citation Articles by Heinecke, J. W. Related Collections Related Webpages Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, S167-S171, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Lipoprotein Metabolism

The HDL proteome: a marker–and perhaps mediator–of coronary artery disease

Jay W. Heinecke¹

Department of Medicine, University of Washington, Seattle, WA 98195

Published, JLR Papers in Press, December 5, 2008.

¹ To whom correspondence should be addressed. e-mail: heinecke{at}u.washington.edu

ABSTRACT

One important cardioprotective function of HDL is to remove cholesterol from lipid-laden macrophages in the artery wall. HDL also exerts anti-inflammatory effects that might inhibit atherogenesis. However, HDL has been proposed to be dysfunctional in humans with established coronary artery disease (CAD), though the underlying mechanisms are unclear. Therefore, we used mass spectrometry to investigate the roles of HDL proteins in inflammation and cardiovascular disease. Shotgun proteomic analysis identified multiple complement regulatory proteins, protease inhibitors, and acute-phase response proteins in HDL, strongly implicating the lipoprotein in inflammation and the innate immune system. Moreover, mass spectrometry and biochemical analyses demonstrated that HDL₃ from subjects with clinically significant CAD was selectively enriched in apolipoprotein E, suggesting that it carries a distinctive protein cargo in humans with atherosclerosis. HDL from CAD subjects also contained markedly elevated levels of chlorotyrosine and nitrotyrosine, two characteristic products of myeloperoxidase, indicating that oxidative damage might generate dysfunctional HDL. Aggressive lipid therapy with a statin and niacin remodeled the HDL proteome to resemble that of apparently healthy subjects. Collectively, our observations indicate that quantifying the HDL proteome by mass spectrometry should help identify novel anti-inflammatory and cardioprotective actions of HDL and provide insights into lipid therapy.

Supplementary key words high density lipoprotein • apolopoprotein E • oxidized high density lipoprotein • C-reactive protein • apolopoprotein A-I • clusterin

Abbreviations: apo, apolipoprotein; CAD, coronary artery disease; MS/MS, tandem mass spectrometry; PLTP, phospholipid transfer protein

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Webpages: