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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 Antioxid+Redox+Signal
2015 ; 22
(18
): 1633-45
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English Wikipedia
Isolevuglandin-type lipid aldehydes induce the inflammatory response of
macrophages by modifying phosphatidylethanolamines and activating the receptor
for advanced glycation endproducts
#MMPMID25751734
Guo L
; Chen Z
; Amarnath V
; Yancey PG
; Van Lenten BJ
; Savage JR
; Fazio S
; Linton MF
; Davies SS
Antioxid Redox Signal
2015[Jun]; 22
(18
): 1633-45
PMID25751734
show ga
AIMS: Increased lipid peroxidation occurs in many conditions associated with
inflammation. Because lipid peroxidation produces lipid aldehydes that can induce
inflammatory responses through unknown mechanisms, elucidating these mechanisms
may lead to development of better treatments for inflammatory diseases. We
recently demonstrated that exposure of cultured cells to lipid aldehydes such as
isolevuglandins (IsoLG) results in the modification of phosphatidylethanolamine
(PE). We therefore sought to determine (i) whether PE modification by
isolevuglandins (IsoLG-PE) occurred in vivo, (ii) whether IsoLG-PE stimulated the
inflammatory responses of macrophages, and (iii) the identity of receptors
mediating the inflammatory effects of IsoLG-PE. RESULTS: IsoLG-PE levels were
elevated in plasma of patients with familial hypercholesterolemia and in the
livers of mice fed a high-fat diet to induce obesity and hepatosteatosis.
IsoLG-PE potently stimulated nuclear factor kappa B (NF?B) activation and
expression of inflammatory cytokines in macrophages. The effects of IsoLG-PE were
blocked by the soluble form of the receptor for advanced glycation endproducts
(sRAGE) and by RAGE antagonists. Furthermore, macrophages derived from the bone
marrow of Ager null mice failed to express inflammatory cytokines in response to
IsoLG-PE to the same extent as macrophages from wild-type mice. INNOVATION: These
studies are the first to identify IsoLG-PE as a mediator of macrophage activation
and a specific receptor, RAGE, which mediates its biological effects. CONCLUSION:
PE modification by IsoLG forms RAGE ligands that activate macrophages, so that
the increased IsoLG-PE generated by high circulating cholesterol levels or
high-fat diet may play a role in the inflammation associated with these
conditions.