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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Pharmacol
2017 ; 8
(ä): 586
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Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced
Macrophage-Derived Foam Cells
#MMPMID28912717
Xu W
; Wei Z
; Dong J
; Duan F
; Chen K
; Chen C
; Liu J
; Yang X
; Chen L
; Xiao H
; Liu A
Front Pharmacol
2017[]; 8
(ä): 586
PMID28912717
show ga
Atherosclerosis (AS) is a chronic disorder of large arteries that is a major risk
factors of high morbidity and mortality. Oxidative modification LDL is one of the
important contributors to atherogenesis. Macrophages take up ox-LDL and convert
into foam cells, which is the hallmark of AS. To advance the understanding of the
metabolic perturbation involved in ox-LDL induced macrophage-derived foam cells
and discover the potential biomarkers of early AS, a global metabolomics approach
was applied based on UHPLC-QTOF/MS. Multivariate statistical analyses identified
five metabolites (25-azacholesterol, anandamide, glycocholate, oleoyl
ethanolamide, and 3-oxo-4, 6-choladienoate) for distinguishing foamy macrophages
from controls. Among the six main metabolic pathways, the unsaturated fatty acid,
especially arachidonic acid metabolism, contributed importantly to early AS. A
new biomarker, anandamide (AEA), whose synthesis and metabolism in macrophages
are disturbed by overloaded ox-LDL, results in metabolic obstruction. This study
is the first to investigate the metabolic disturbance in macrophage-derived foam
cells induced by ox-LDL and screen potential biomarkers and metabolic pathways
associated with early AS. Our findings provide a new insight in the underlying
pathophysiological mechanisms and also help to identify novel targets for the
intervention of AS.