Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
Language: 
English
Abstract: 

12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs. LDLr knockout (SK) mice fed a PUFA-enriched diet to enhance production of 12/15LO products. Compared with SK controls, DK mice fed a PUFA-enriched diet had decreased plasma and liver lipid levels, hepatic lipogenic gene expression, VLDL secretion, and aortic atherosclerosis and increased VLDL turnover. Bone marrow transplantation and Kupffer cell ablation studies suggested both circulating leukocytes and Kupffer cells contributed to the lipid phenotype in 12/15LO-deficient mice. Conditioned medium from in vitro incubation of DK vs. SK macrophages reduced triglyceride secretion in McArdle 7777 hepatoma cells. Our results suggest that, in the context of dietary PUFA enrichment, macrophage 12/15LO expression adversely affects plasma and hepatic lipid metabolism, resulting in exacerbated atherosclerosis.

Author(s): 
Rong, Shunxing
Cao, Qiang
Liu, Mingxia
Seo, Jeongmin
Jia, Lin
Boudyguina, Elena
Gebre, Abraham K.
Colvin, Perry L.
Smith, Thomas L.
Murphy, Robert C.
Mishra, Nilamadhab
Parks, John S.
Item Type: 
Journal Article
Publication Title: 
Journal of Lipid Research
Journal Abbreviation: 
J. Lipid Res.
Publication Date: 
Apr 2012
Publication Year: 
2012
Pages: 
686-695
Volume: 
53
Issue: 
4
ISSN: 
0022-2275
DOI: 
10.1194/jlr.M022723
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22279185 PMCID: PMC3307645

Turabian/Chicago Citation

Shunxing Rong, Qiang Cao, Mingxia Liu, Jeongmin Seo, Lin Jia, Elena Boudyguina, Abraham K. Gebre, Perry L. Colvin, Thomas L. Smith, Robert C. Murphy, Nilamadhab Mishra and John S. Parks. Apr 2012. "Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis." Journal of Lipid Research 53: 4: 686-695. 10.1194/jlr.M022723.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1194/jlr.M022723 | issn = 0022-2275 | volume = 53 | pages = 686-695 | last = Rong | first = Shunxing | coauthors = Cao, Qiang, Liu, Mingxia, Seo, Jeongmin, Jia, Lin, Boudyguina, Elena, Gebre, Abraham K., Colvin, Perry L., Smith, Thomas L., Murphy, Robert C., Mishra, Nilamadhab, Parks, John S. | title = Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis | journal = Journal of Lipid Research | date = Apr 2012 | pmid = | pmc = }} </ref>