TY - JOUR
T1 - Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration
AU - Kim, Jeonghan
AU - Ko, Jesang
N1 - Publisher Copyright:
© FASEB.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Atherosclerosis is a chronic inflammatory response of the vascular wall, and immune responses are involved in every phase of atherosclerosis, from initiation, to progression, and finally to plaque rupture. Cytokines are the major atherogenic mediators that promote plaque formation and progression by activation of inflammatory cells. They induce expressions of matrix metalloproteinases (MMPs), leading to vascular smooth muscle cell (VSMC) migration in atherosclerotic lesions. Although chronic inflammatory mediators, including tumor necrosis factor α (TNF-α) and MMPs, exacerbate atherosclerosis, the molecular mechanism of atherogenesis remains unclear. In this study we investigated the role of a novel transcription factor the human small leucine zipper protein (sLZIP) in TNF-α-induced MMP expression, VSMC migration, and atherosclerosis progression. The proinflammatory cytokine TNF-αenhanced sLZIP expression by 3-fold via activation of NF-κB signaling. sLZIP induced MMP-9 transcription and the proteolytic activity of MMP-9 by 2.8- and 3.2-fold (P< 0.05), respectively, in macrophages, leading to enhancement of VSMC migration by 2.7-fold (P<0.005). sLZIPOE/+(sLZIP transgenic); LDLR-/- mice fed a high-cholesterol diet exhibited enhanced arterial plaque formation and increased VSMC migration from the media into the intima by 2.8- and 2.6-fold (P<0.01), respectively, compared with atherosclerosis-prone LDLR-/- mice. These results indicate that human sLZIP plays a critical role in development of atherosclerosis and can be used as a therapeutic target molecule for treatment of atherosclerosis.- Kim, J., Ko, J. Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration.
AB - Atherosclerosis is a chronic inflammatory response of the vascular wall, and immune responses are involved in every phase of atherosclerosis, from initiation, to progression, and finally to plaque rupture. Cytokines are the major atherogenic mediators that promote plaque formation and progression by activation of inflammatory cells. They induce expressions of matrix metalloproteinases (MMPs), leading to vascular smooth muscle cell (VSMC) migration in atherosclerotic lesions. Although chronic inflammatory mediators, including tumor necrosis factor α (TNF-α) and MMPs, exacerbate atherosclerosis, the molecular mechanism of atherogenesis remains unclear. In this study we investigated the role of a novel transcription factor the human small leucine zipper protein (sLZIP) in TNF-α-induced MMP expression, VSMC migration, and atherosclerosis progression. The proinflammatory cytokine TNF-αenhanced sLZIP expression by 3-fold via activation of NF-κB signaling. sLZIP induced MMP-9 transcription and the proteolytic activity of MMP-9 by 2.8- and 3.2-fold (P< 0.05), respectively, in macrophages, leading to enhancement of VSMC migration by 2.7-fold (P<0.005). sLZIPOE/+(sLZIP transgenic); LDLR-/- mice fed a high-cholesterol diet exhibited enhanced arterial plaque formation and increased VSMC migration from the media into the intima by 2.8- and 2.6-fold (P<0.01), respectively, compared with atherosclerosis-prone LDLR-/- mice. These results indicate that human sLZIP plays a critical role in development of atherosclerosis and can be used as a therapeutic target molecule for treatment of atherosclerosis.- Kim, J., Ko, J. Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration.
KW - Atherosclerosis
KW - Macrophage
KW - Matrix metalloproteinase
KW - SLZIP
KW - Vascular smooth muscle cell
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U2 - 10.1096/fj.14-259218
DO - 10.1096/fj.14-259218
M3 - Article
C2 - 25077563
AN - SCOPUS:84912050595
VL - 28
SP - 5010
EP - 5021
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 1530-6860
IS - 11
ER -