| Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. | |
| | |
MedLine Citation:
|
PMID: 21957201 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The generation of oxidized phospholipids in lipoproteins has been linked to vascular inflammation in atherosclerotic lesions. Products of phospholipid oxidation increase endothelial activation, however their effects on macrophages are poorly understood and it is unclear whether these effects are regulated by the biochemical pathways that metabolize oxidized phospholipids. We found that incubation of 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) with THP-1-derived macrophages up-regulated the expression of cytokine genes including GM-CSF, TNF-α, MCP-1, IL-1β, IL-6, and IL-8. In these cells, reagent POVPC was either hydrolyzed to lyso-phosphatidylcholine (lyso-PC) or reduced to 1-palmitoyl-2-(5-hydroxy-valeroyl)-sn-glycero-3-phosphocholine (PHVPC). Treatment with the phospholipase A2 (PLA2) inhibitor, pefabloc, decreased POVPC hydrolysis and increased PHVPC accumulation. Pefabloc also increased the induction of cytokine genes in POVPC-treated cells. In contrast, PHVPC accumulation and cytokine production were decreased upon treatment with the aldose reductase (AR) inhibitor, tolrestat. In comparison with POVPC, lyso-PC led to 2-3-fold greater and PHVPC 10-100-fold greater induction of cytokine genes. POVPC-induced cytokine gene induction was prevented in bone-marrow derived macrophages from AR-null mice. These results indicate that although hydrolysis is the major pathway of metabolism, reduction further increases the pro-inflammatory responses to POVPC. Thus, vascular inflammation in atherosclerotic lesions is likely to be regulated by metabolism of phospholipid aldehydes in macrophages. |
| | |
Authors:
|
Elena Vladykovskaya; Evgeny Ozhegov; J David Hoetker; Zhengzhi Xie; Yonis Ahmed; Jill Suttles; Sanjay Srivastava; Aruni Bhatnagar; Oleg A Barski |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-9-27 |
Journal Detail:
|
Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-9-29 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Louisville, United States. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: LDL-apheresis depletes apoE-HDL and pre{beta}-1 HDL in Familial Hypercholesterolemia : Relevance to ...
Next Document: Nascent HDL formation by hepatocytes is reduced by the concerted action of serum amyloid A and endot...