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PMID: 22935534 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Role of phospholipid oxidation products in atherosclerosis.

Circulation research ·Vol. 111 ·No. 6 ·2012-08-31 ·Pages 778-99

Lee S, Birukov KG, Romanoski CE, Springstead JR, Lusis AJ, Berliner JA

Abstract

There is increasing clinical evidence that phospholipid oxidation products (Ox-PL) play a role in atherosclerosis. This review focuses on the mechanisms by which Ox-PL interact with endothelial cells, monocyte/macrophages, platelets, smooth muscle cells, and HDL to promote atherogenesis. In the past few years major progress has been made in identifying these mechanisms. It has been recognized that Ox-PL promote phenotypic changes in these cell types that have long-term consequences for the vessel wall. Individual Ox-PL responsible for specific cellular effects have been identified. A model of the configuration of bioactive truncated Ox-PL within membranes has been developed that demonstrates that the oxidized fatty acid moiety protrudes into the aqueous phase, rendering it accessible for receptor recognition. Receptors and signaling pathways for individual Ox-PL species are now determined and receptor independent signaling pathways identified. The effects of Ox-PL are mediated both by gene regulation and transcription independent processes. It has now become apparent that Ox-PL affects multiple genes and pathways, some of which are proatherogenic and some are protective. However, at concentrations that are likely present in the vessel wall in atherosclerotic lesions, the effects promote atherogenesis. There have also been new insights on enzymes that metabolize Ox-PL and the significance of these enzymes for atherosclerosis. With the knowledge we now have of the regulation and effects of Ox-PL in different vascular cell types, it should be possible to design experiments to test the role of specific Ox-PL on the development of atherosclerosis.

MeSH Terms
Atherosclerosis/metabolism Cytokines/metabolism Endothelial Cells/metabolism Humans Macrophages/metabolism Myocytes, Smooth Muscle/metabolism Oxidation-Reduction Phospholipids/metabolism Receptors, Cell Surface/metabolism Signal Transduction
Chemicals
Cytokines Phospholipids Receptors, Cell Surface
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lee Sangderk
Department of Pathology, University of California-Los Angeles, MRL 4760, 675 Charles E. Young Dr. S., Los Angeles, CA 90095, USA.
Birukov Konstantin G
Romanoski Casey E
Springstead James R
Lusis Aldons J
Berliner Judith A
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Article Info
Journal
Circulation research
Abbr.
Circ Res
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.111.256859
Published
2012-08-31
Pages
778-99
Language
English
Region
United States
NLM ID
0047103
PMCID
PMC3563283
Subset
IM
Grants
NHLBI NIH HHS · 1K99HL105577 · United States
NHLBI NIH HHS · R00 HL105577 · United States
NHLBI NIH HHS · HL064731 · United States
NHLBI NIH HHS · HL30568 · United States
NHLBI NIH HHS · HL87823 · United States
NHLBI NIH HHS · R01 HL087823 · United States
NHLBI NIH HHS · P01 HL030568 · United States
NHLBI NIH HHS · T32 HL069766 · United States
NHLBI NIH HHS · T232HL69766 · United States
NHLBI NIH HHS · P01 HL058064 · United States
NHLBI NIH HHS · R01 HL076259 · United States
NHLBI NIH HHS · HL76259 · United States
NHLBI NIH HHS · R01 HL064731 · United States
NHLBI NIH HHS · K99 HL105577 · United States
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PubMed source DOI: 10.1161/CIRCRESAHA.111.256859 PMC Full Text View journal details
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