Interferon regulatory factor-1 exerts inhibitory effect on neointimal formation after vascular injury.
OBJECTIVE
To investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.


METHODS
Vascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin II type 2 (AT2) receptor, interleukin-1 beta converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.


RESULTS
Neointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.


CONCLUSIONS
Our results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis in VSMCs.
Li
Zhen
Z
Vascular Surgery, the Second Artillery General Hospital, Beijing 100088, China. zhenli0328@hotmail.com
Wang
Zhong-gao
ZG
Bian
Ce
C
Chen
Xiao-dong
XD
Li
Jian-wen
JW
Chen
Xiu
X
Han
Bing
B
Hou
Gao-feng
GF
Chu
Jian
J
Cui
Qi
Q
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D005263:Femoral Artery / Q000033:anatomy & histology / Q000473:pathology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology
D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D044139:Receptor, Angiotensin, Type 2; D052247:Nitric Oxide Synthase Type II; D020170:Caspase 1