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Research Article Free access | 10.1172/JCI118359

Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.

A D Watson, J A Berliner, S Y Hama, B N La Du, K F Faull, A M Fogelman, and M Navab

Department of Pathology, University of California, Los Angeles 90095-1732, USA.

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Department of Pathology, University of California, Los Angeles 90095-1732, USA.

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Department of Pathology, University of California, Los Angeles 90095-1732, USA.

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Department of Pathology, University of California, Los Angeles 90095-1732, USA.

Find articles by La Du, B. in: JCI | PubMed | Google Scholar

Department of Pathology, University of California, Los Angeles 90095-1732, USA.

Find articles by Faull, K. in: JCI | PubMed | Google Scholar

Department of Pathology, University of California, Los Angeles 90095-1732, USA.

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Department of Pathology, University of California, Los Angeles 90095-1732, USA.

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Published December 1, 1995 - More info

Published in Volume 96, Issue 6 on December 1, 1995
J Clin Invest. 1995;96(6):2882–2891. https://doi.org/10.1172/JCI118359.
© 1995 The American Society for Clinical Investigation
Published December 1, 1995 - Version history
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Abstract

Our group has previously demonstrated that oxidized phospholipids in mildly oxidized LDL (MM-LDL) produced by oxidation with lipoxygenase, iron, or cocultures of artery wall cells increase monocyte-endothelial interactions and this sequence of events is blocked by HDL. To obtain further insight into the mechanism by which HDL abolishes the activity of MM-LDL we investigated the effect of the HDL-associated ester hydrolase paraoxonase (PON). Treatment of MM-LDL with purified PON significantly reduced the ability of MM-LDL to induce monocyte-endothelial interactions. Inactivation of PON by pretreating HDL with heat or EDTA reduced the ability of HDL to inhibit LDL modification. HPLC analysis of phospholipids isolated from MM-LDL before and after treatment with purified PON showed that the 270 nm absorbance of phospholipids was decreased, while no effect was observed on 235 nm absorbance. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and specific fractions of Ox-PAPC isolated by HPLC induced the same monocyte-endothelial interactions as did MM-LDL. Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC. Comparison of Ox-PAPC by fast atom bombardment-mass spectrometry before and after PON treatment showed that PON destroyed these multi-oxygenated molecules found in biologically active fractions of Ox-PAPC. These results suggest that PON in HDL may protect against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in mildly oxidized LDL.

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