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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 Int+J+Mol+Med
2017 ; 40
(2
): 558-568
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gab.com Text
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Macrophage-derived foam cells impair endothelial barrier function by inducing
endothelial-mesenchymal transition via CCL-4
#MMPMID28656247
Yang Y
; Luo NS
; Ying R
; Xie Y
; Chen JY
; Wang XQ
; Gu ZJ
; Mai JT
; Liu WH
; Wu MX
; Chen ZT
; Fang YB
; Zhang HF
; Zuo ZY
; Wang JF
; Chen YX
Int J Mol Med
2017[Aug]; 40
(2
): 558-568
PMID28656247
show ga
Recently, endothelial-mesenchymal transition (EndMT) has been demonstrated to
play an important role in the development of atherosclerosis, the molecular
mechanisms of which remain unclear. In the present study, scanning electron
microscopy directly revealed a widened endothelial space and
immunohistofluorescence demonstrated that EndMT was increased in human aorta
atherosclerotic plaques. M1 macrophage-derived foam cell (M1-FC) supernatants,
but not M2 macrophage-derived foam cell (M2-FC) supernatants, induced EndMT. A
protein array and enzyme-linked immunosorbent assay identified that the levels of
several cytokines, including C-C motif chemokine ligand 4 (CCL-4) were increased
in M1-FC supernatants, in which EndMT was promoted, accompanied by increased
endothelial permeability and monocyte adhesion. Furthermore, anti-CCL-4 antibody
abolished the effects of M1-FC supernatants on EndMT. At the same time, CCL-4
activated its receptor, C-C motif chemokine receptor-5 (CCR-5), and upregulated
transforming growth factor-? (TGF-?) expression. Further experiments revealed
that EndMT induced by CCL-4 was reversed by treatment with CCR-5 antagonist and
the RNA-mediated knockdown of TGF-?. On the whole, the data of the present study
suggest that M1-FCs induce EndMT by upregulating CCL-4, and increase endothelial
permeability and monocyte adhesion. These data may help to elucidate the
important role of EndMT in the development of atherosclerosis.