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Identification of alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine molecular species in human atherosclerotic lesions.

Abstract：

BACKGROUND:A role for myeloperoxidase (MPO) as a mediator of coronary artery disease and acute coronary syndromes has recently received considerable attention. Although active MPO and hypochlorite-modified proteins and peptides have been detected in human atherosclerotic lesions, detection of novel chlorinated oxidized lipid species with proatherogenic properties in vivo has not yet been reported. In this study we show that MPO-generated reactive chlorinating species promote selective oxidative cleavage of plasmalogens, liberating alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine in human atherosclerotic lesions. METHODS AND RESULTS:Stable isotope dilution gas chromatography-mass spectrometry methods were used to identify and quantitate the alpha-chloro fatty aldehyde, 2-chlorohexadecanal, in atherosclerotic versus normal human aorta. Compared with normal aorta, 2-chlorohexadecanal levels were elevated more than 1400-fold in atherosclerotic tissues. Parallel electrospray ionization mass spectrometry studies confirmed 34- and 20-fold increases in the plasmalogen cooxidation products, unsaturated lysophosphatidylcholine molecular species containing linoleic and arachidonic acid, respectively, within atherosclerotic compared with normal aorta. Unsaturated lysophosphatidylcholine containing docosahexaenoic acid was also detected in atherosclerotic but not in normal aorta. Exposure of primary human coronary artery endothelial cells to plasmalogen-derived lysophosphatidylcholine molecular species produced marked increases in P-selectin surface expression. CONCLUSIONS:The present studies demonstrate that plasmalogens are attacked by MPO-derived reactive chlorinating species within human atheroma. The resultant species formed, alpha-chloro fatty aldehydes and unsaturated lysophospholipids, possess proatherogenic properties, as shown by induction of P-selectin surface expression in primary human coronary artery endothelial cells.

journal_name

Circulation

journal_title

Circulation

authors

Thukkani AK,McHowat J,Hsu FF,Brennan ML,Hazen SL,Ford DA

doi

10.1161/01.CIR.0000104564.01539.6A

subject

Has Abstract

pub_date

2003-12-23 00:00:00

pages

3128-33

issue

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000104564.01539.6A

journal_volume

108

pub_type

杂志文章

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Identification of alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine molecular species in human atherosclerotic lesions.