Zhicheng Zhu1, Rihao Xu1, Xiaomei Zheng1, Tiance Wang1, Dan Li1, Yong Wang1, Kexiang Liu2. 1. Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China. 2. Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, China liukxkxy@126.com.
Abstract
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.
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.