[Role of toll like receptor 4 in low shear stress-induced intimal hyperplasia].
OBJECTIVE
To determine the role of toll like receptor 4 (TLR4) in intimal hyperplasia induced by low shear stress (LSS).


METHODS
TLR4(-/-) mice and control mice C57BL/6J were used. Polyethylene cuff was placed on murine carotid to establishing a LSS model. Cultured vascular endothelial cells under LSS condition were used as an in vitro LSS cell model. Intimal hyperplasia was evaluated pathologically. TLR4 was tested by Western blot and the expression of IL-1β, IL-6 and TNF-α mRNA were detected using RT-PCR. Cell proliferation was determined by detecting DNA synthesis.


RESULTS
LSS elicited significant carotid intimal hyperplasia in normal mice but a slight neointima formation in TLR4(-/-) mice (42.67 ± 16.46 vs 7.03 ± 2.95, P < 0.05). LSS upregulated the expression of TLR4 (2.30 ± 0.66 vs 0.16 ± 0.10, P < 0.05), as well as the mRNA of IL-1β (6.52 ± 3.15 vs 1.65 ± 0.45, P < 0.01), IL-6 (16.17 ± 7.49 vs 6.50 ± 1.84, P < 0.01) and TNF-α(9.98 ± 3.77 vs 2.72 ± 1.03, P < 0.01) in normal mice. However, only moderate increases in IL-6 and TNF-α mRNA were observed in TLR4(-/-) mice. LSS induced the proliferation in cultured endothelial cells. And it was further enhanced by TLR4 overexpression (177 ± 33 vs 83 ± 15, P < 0.05) but attenuated by TLR4 silencing (40 ± 8 vs 83 ± 15, P < 0.05).


CONCLUSIONS
TLR4 plays an important role in LSS-induced intimal hyperplasia. It is likely that LSS induces the proliferation of endothelial cells through TLR4-mediated inflammatory reaction and ultimately promotes intimal hyperplasia.
Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Bing-hu
BH
Li
Li-li
LL
Zhang
Yan
Y
Pi
Yan-wei
YW
Yin
Qing-wu
QW
Yang
Chuan-qin
CQ
Fang
Chang-yue
CY
Gao
Jing-cheng
JC
Li
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013314:Stress, Mechanical; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4