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J Lipid Res. 2017 Oct;58(10):1999-2007. doi: 10.1194/jlr.M077792. Epub 2017 Aug 16.

Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis.

Author information

1
Department of Chemistry University of Connecticut, Storrs, CT 06269.
2
Department of Immunology and Medicine, University of Connecticut School of Medicine, Farmington, CT 06030.
3
Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905.
4
Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT 06030.
5
Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142 and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
6
Infectious Disease Division, Veterans Affairs Medical Center, Los Angeles, CA 90073 and Departments of Medicine and Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90024.
7
Hartford Healthcare Medical Group, Hartford, CT 06106.
8
Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269.
9
Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT 06030 Nichols@nso.uchc.edu.

Abstract

Multiple reaction monitoring-MS analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes, including Lipid 654, an agonist for human and mouse Toll-like receptor (TLR)2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes and human serum and brain samples from healthy adults. The median Lipid 430/Lipid 654 ratio observed in carotid endarterectomy samples was significantly higher than the median ratio in lipid extracts of common oral and intestinal Bacteroidetes bacteria, and serum and brain samples from healthy subjects. More importantly, the median Lipid 430/Lipid 654 ratio was significantly elevated in carotid endarterectomies when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls.

KEYWORDS:

Toll like receptors; atherosclerosis; mass spectrometry; phospholipase A2

PMID:
28814639
PMCID:
PMC5625123
DOI:
10.1194/jlr.M077792
[Indexed for MEDLINE]
Free PMC Article

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