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Inhibitory Effect of TLR4 Gene Silencing on Intimal Hyperplasia of Vein Grafting
Author(s) -
Zhicheng Zhu,
Rihao Xu,
Xiaoliang Zheng,
Tiance Wang,
Dan Li,
Yong Wang,
Kexiang Liu
Publication year - 2016
Publication title -
vascular and endovascular surgery/vascular and endovascular surgery
Language(s) - English
Resource type - Journals
eISSN - 1938-9116
pISSN - 1538-5744
DOI - 10.1177/1538574416670308
Subject(s) - intimal hyperplasia , medicine , gene silencing , tlr4 , small interfering rna , hyperplasia , jugular vein , vein , artery , transfection , pathology , inflammation , cancer research , surgery , immunology , biology , cell culture , gene , biochemistry , genetics , smooth muscle
Purpose: 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.Conclusion: 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.

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