Formation of dysfunctional high-density lipoprotein by myeloperoxidase

Stephen J. Nicholls, Lemin Zheng, Stanley L. Hazen

Research output: Contribution to journalReview ArticleResearchpeer-review

129 Citations (Scopus)

Abstract

Recent studies identify the presence of high-density lipoprotein (HDL) particles in patients with cardiovascular disease, which are "dysfunctional," lacking in typical atheroprotective properties, and promoting proinflammatory effects. The mechanisms for generating dysfunctional HDL have been unclear. New evidence points to a role for myeloperoxidase (MPO)-generated oxidants as participants in rendering HDL dysfunctional within human atherosclerotic plaque. Myeloperoxidase was recently shown to bind to HDL within human atherosclerotic lesions, and biophysical studies reveal MPO binding occurs via specific interactions with apolipoprotein (apo) A-I, the predominant protein of HDL. This likely facilitates the observed selective targeting of apoA-I for site-specific chlorination and nitration by MPO-generated reactive oxidants in vivo. One apparent consequence of MPO-catalyzed apoA-I oxidation includes the functional impairment of the ability of HDL to promote cellular cholesterol efflux via the adenosine triphosphate binding cassette-1 transport system. Myeloperoxidase-mediated loss of the atheroprotective functional properties of HDL may thus provide a novel mechanism linking inflammation and oxidative stress to the pathogenesis of atherosclerosis.

Original languageEnglish
Pages (from-to)212-219
Number of pages8
JournalTrends in Cardiovascular Medicine
Volume15
Issue number6
DOIs
Publication statusPublished - 1 Aug 2005
Externally publishedYes

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