Inhibitory Effect of TLR4 Gene Silencing on Intimal Hyperplasia of Vein Grafting.
OBJECTIVE
The present study aimed to explore the regulating effect of Toll-like receptor 4 (TLR4) on intimal hyperplasia in rat vein grafts.


METHODS
Rat models of external jugular vein carotid artery bypass grafting were established. Afterward, TLR4 small interfering RNA (siRNA) recombinant plasmids were constructed, which were transfected into rat vein graft bypass to study the effect of TLR4 silencing on intimal hyperplasia and to explore the underlying mechanisms. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of TLR4 and inflammatory factors in TLR4 siRNA-transfected vein graft bypass. The intimal thickness was evaluated using hematoxylin-eosin staining.


RESULTS
Compared with the scramble siRNA group, the intimal thickness of vein grafting was decreased significantly, while the inflammatory factors including interleukin (IL) 1β, IL-6, and tumor necrosis factor α in grafted vein were dramatically downregulated in the TLR4 siRNA group.


CONCLUSIONS
These results showed that local silencing of TLR4 in the vein grafts could inhibit intimal hyperplasia by downregulating the expression of inflammatory factors in the vein grafts, suggesting that TLR4 can be used as a new target for therapy of vascular intimal hyperplasia.
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Zhicheng
Z
Zhu
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Rihao
R
Xu
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Xiaomei
X
Zheng
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Tiance
T
Wang
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Dan
D
Li
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Yong
Y
Wang
Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China liukxkxy@126.com.
Kexiang
K
Liu
D000818:Animals; D017536:Carotid Artery, Common / Q000601:surgery*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007601:Jugular Veins / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008297:Male; D058426:Neointima; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D058017:Vascular Grafting / Q000009:adverse effects*
C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D034741:RNA, Small Interfering; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha

TLR4
; inflammatory factors; intimal hyperplasia; vein grafts