Abstract:
PURPOSE OF REVIEW:Unregulated uptake of oxidized LDL by macrophages to form foam cells is the hallmark for atherosclerosis. The paraoxonase (PON) family of enzymes plays a critical role in attenuating atherosclerotic lesion formation by hydrolyzing lipid peroxides (LOOHs) and preventing the oxidation of LDL particles and by enhancing HDL-mediated cholesterol efflux. Findings in recent years suggest novel mechanisms by which PON isoforms interact with macrophages to regulate cholesterol metabolism and cellular function. RECENT FINDINGS:The association of PON with HDL particles facilitates binding of the particle to macrophages and ABCA1-dependent cholesterol efflux. The hydrolysis of membrane phospholipids by PON generates lysophosphatidylcholine which is shown to regulate expression of cholesterol transport proteins. The PON family also regulates multiple aspects of macrophage function. PON attenuates inflammation and prevents induction of apoptosis via activation of a scavenger receptor class B type-1-dependent signaling mechanism. PON limits macrophage-dependent oxidant formation by preventing the activation of the membrane-associated NADPH oxidase and by stabilizing mitochondria. PON also promotes the differentiation of macrophages to an anti-inflammatory phenotype. This function appears to be independent of PON enzymatic activity and, rather, is dependent on the ability of endogenous sulfhydryls to neutralize pro-inflammatory peroxides. SUMMARY:In recent years, the therapeutic efficacy of HDL-based therapies has been subject to dispute. Pharmacological approaches that target an increase in the expression and/or activity of PON may facilitate macrophage cholesterol metabolism and attenuate inflammatory injury.
journal_name
Curr Opin Lipidoljournal_title
Current opinion in lipidologyauthors
White CR,Anantharamaiah GMdoi
10.1097/MOL.0000000000000444subject
Has Abstractpub_date
2017-10-01 00:00:00pages
397-402issue
5eissn
0957-9672issn
1473-6535journal_volume
28pub_type
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
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journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
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更新日期:2004-10-01 00:00:00
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journal_title:Current opinion in lipidology
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