Objective: Whether single low shear stress can result in atherosclerosis without hyperliposis-diet in vivo or not is unknown. Methods: Based on an electromagnetic blood flow meter and a method to determine the pulsati...Objective: Whether single low shear stress can result in atherosclerosis without hyperliposis-diet in vivo or not is unknown. Methods: Based on an electromagnetic blood flow meter and a method to determine the pulsatile shear stress from blood flow rate waveform and its software,we developed an in vivo pulsatile blood flow rate-shear stress determining system.The left external carotid arteries of 20 adult New Zealand white rabbits were ligated and the rabbits were fed with a standard chow for 2,4,8 or 12 weeks,then the common carotid arteries of 2 sides in each rabbit were harvested for morphologic test. Results: The ligation reduced pulsatile shear stress of left common carotid significantly,for example,τ_ mean changed from(21.16±7.17) dynes/cm 2 to(3.13±2.28) dynes/cm 2(p=2.176E-21),meanwhile,the pulsatile shear stress of right common carotid did not change significantly,which lasted more than 12 weeks.Atherosclerotic plaques were found after 8 and 12 weeks in pulsatile-low-shear-stress left(not normal-shear-stress right) common carotid arteries.Conclusion:Single pulsatile low shear stress can result in atherosclerosis.It supports the pulsatile low shear stress(not hypolipidemia) is the key risk factor for atherosclerosis.展开更多
Instruction Shear stress,caused by the parallel frictional drag force of blood flow,is a biomechanical force which plays an important role in the control of blood vessels growth and functions [1]. Clinical researches ...Instruction Shear stress,caused by the parallel frictional drag force of blood flow,is a biomechanical force which plays an important role in the control of blood vessels growth and functions [1]. Clinical researches had found out that atherosclerotic le-展开更多
Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important r...Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development.In the process of inflammatory reaction,the damage of vascular endothelial cells is the initial link,and various factors can cause damage of endothelial cells.The change of shear stress is considered to be one of the important factors.In the body,vascular endothelial cells are constantly exposed to blood flow.Flow conditions critically regulate endothelial cell functions in the vasculature.Shear stress not only influences the endothelial cell morphology,migration,differentiation and proliferation,but also regulates the expression of proteins in the endothelial cells.Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions and promote the formation of atherosclerosis.In the present study,the objective of our study is the comprehensive identification of CX3CR1/NF-κB signaling pathway involved in low shear stress(LSS)-induced inflammation in HUVECs through protein profiling and cell function experiment.Methods Human umbilical vein endothelial cell was cultured onglass slides and placed in a parallel plate flow chamber.M199 culture medium was used for low laminar shear stress at 4.14 dyn/cm2,2 h for the testing group,CX3CR1 sh-RNA and NF-κB inhibitor PDTC are used to block the effects of CX3CR1 and P65.The expression levels of the protein were determined by western blot analysis.Mononuclear cell adhesion assays and scratch assays are used to detect cell adhesion and migration.Results Western blotting analyses revealed that compared with the controls,there is a significant increase in the expression of CX3CR1,nucleusP65,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and Interleukin-6(IL-6),while the expression of cytosolic P65 and IκB was significantly reduced in human umbilical vein endothelial cells(HUVECs)treated with LSS.CX3CR1 Sh-RNA was use to reveal its effect on LSS-induced inflammation.Further,specific NF-κB P65 inhibitors(PDTC)were used to reveal the downstream NF-κB P65 exclusively involved in LSS-induced inflammation in HUVECs,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.Monocyte adhesion assay and scratch test revealed LSS promotes adhesion of monocytes and migration of cells,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.LSS is involved in the expression of adhesion moleculesand chemokines,which are important for the initiation of endothelial inflammation-related atherosclerosis.Conclusions The activation of CX3CR1/NF-κB signaling pathway induced by low shear stress in endothelial cells may lead to the future therapeutic targets of atherosclerotic inflammation.展开更多
月球的低重力环境对月面浅层月壤力学特性的影响很大。利用清华大学取自吉林省靖宇县境内的火山灰岩研制出的模拟月壤（QH-E）,对GCTS公司生产的STX型动/应力路径三轴仪重新配置高精度的传感器,并采取专门的试验技术,成功实施了一系列...月球的低重力环境对月面浅层月壤力学特性的影响很大。利用清华大学取自吉林省靖宇县境内的火山灰岩研制出的模拟月壤（QH-E）,对GCTS公司生产的STX型动/应力路径三轴仪重新配置高精度的传感器,并采取专门的试验技术,成功实施了一系列低围压水平（3.13~25 k Pa）的三轴压缩试验。试验结果表明,在低围压水平下：模拟月壤具有显著的剪胀效应;与常规围压水平（50~150 k Pa）结果相比,同一相对密度模拟月壤的峰值摩擦角更高;相对密度越高,峰值摩擦角越大;切线模量和剪切模量均随着围压和相对密度的减小而减小;剪胀角随围压的减小和相对密度的增大而增大,且低围压水平下剪胀角对围压变化十分敏感。最后就低围压下QH-E模拟月壤与饱和砂土特性的差异,及重力场环境和施加围压的介质的影响进行了讨论。展开更多
目的建立一种可调控的兔颈动脉切应力及低密度脂蛋白(low density lipoprotein,LDL)浓度极化动物模型,初步观察二者对动脉粥样硬化(artherosclerosis,AS)形成的影响。方法兔左颈总动脉施以3个狭窄度(30%、40%、50%)的硅胶管环扎手术,以...目的建立一种可调控的兔颈动脉切应力及低密度脂蛋白(low density lipoprotein,LDL)浓度极化动物模型,初步观察二者对动脉粥样硬化(artherosclerosis,AS)形成的影响。方法兔左颈总动脉施以3个狭窄度(30%、40%、50%)的硅胶管环扎手术,以右颈总动脉为假手术对照;饲喂含4种不同胆固醇浓度(0%、0.5%、1%、1.5%)饲料;彩色超声检测双侧颈总动脉血流动力学参数,计算切应力值,血管标本行病理及扫描电镜观察。结果同一狭窄度,左颈总动脉切应力随饲喂饲料所含胆固醇浓度的增加而增加;同一胆固醇浓度,左颈总动脉切应力以40%狭窄度组最低;同一样本,左颈总动脉切应力高于右颈总动脉(P<0.05)。病理切片及扫描电镜检测显示各组动物左颈总动脉均出现不同程度的AS病变,以40%狭窄度组病变更为显著。结论成功建立了可调控的兔颈总动脉切应力及LDL浓度极化模型,低切应力及LDL浓度极化促进AS的形成和发展。展开更多
文摘Objective: Whether single low shear stress can result in atherosclerosis without hyperliposis-diet in vivo or not is unknown. Methods: Based on an electromagnetic blood flow meter and a method to determine the pulsatile shear stress from blood flow rate waveform and its software,we developed an in vivo pulsatile blood flow rate-shear stress determining system.The left external carotid arteries of 20 adult New Zealand white rabbits were ligated and the rabbits were fed with a standard chow for 2,4,8 or 12 weeks,then the common carotid arteries of 2 sides in each rabbit were harvested for morphologic test. Results: The ligation reduced pulsatile shear stress of left common carotid significantly,for example,τ_ mean changed from(21.16±7.17) dynes/cm 2 to(3.13±2.28) dynes/cm 2(p=2.176E-21),meanwhile,the pulsatile shear stress of right common carotid did not change significantly,which lasted more than 12 weeks.Atherosclerotic plaques were found after 8 and 12 weeks in pulsatile-low-shear-stress left(not normal-shear-stress right) common carotid arteries.Conclusion:Single pulsatile low shear stress can result in atherosclerosis.It supports the pulsatile low shear stress(not hypolipidemia) is the key risk factor for atherosclerosis.
基金supported by grants from the National Natural Science Foundation of China,Nos10732070,10702043,30970703,10972140 and 30470432
文摘Instruction Shear stress,caused by the parallel frictional drag force of blood flow,is a biomechanical force which plays an important role in the control of blood vessels growth and functions [1]. Clinical researches had found out that atherosclerotic le-
基金supported by a project grant from the National Natural Science Foundation of China ( 31860261)
文摘Background Cardiovascular disease has become a major cause of death worldwide.Atherosclerosis is the pathological basis of many cardiovascular diseases.It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development.In the process of inflammatory reaction,the damage of vascular endothelial cells is the initial link,and various factors can cause damage of endothelial cells.The change of shear stress is considered to be one of the important factors.In the body,vascular endothelial cells are constantly exposed to blood flow.Flow conditions critically regulate endothelial cell functions in the vasculature.Shear stress not only influences the endothelial cell morphology,migration,differentiation and proliferation,but also regulates the expression of proteins in the endothelial cells.Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions and promote the formation of atherosclerosis.In the present study,the objective of our study is the comprehensive identification of CX3CR1/NF-κB signaling pathway involved in low shear stress(LSS)-induced inflammation in HUVECs through protein profiling and cell function experiment.Methods Human umbilical vein endothelial cell was cultured onglass slides and placed in a parallel plate flow chamber.M199 culture medium was used for low laminar shear stress at 4.14 dyn/cm2,2 h for the testing group,CX3CR1 sh-RNA and NF-κB inhibitor PDTC are used to block the effects of CX3CR1 and P65.The expression levels of the protein were determined by western blot analysis.Mononuclear cell adhesion assays and scratch assays are used to detect cell adhesion and migration.Results Western blotting analyses revealed that compared with the controls,there is a significant increase in the expression of CX3CR1,nucleusP65,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and Interleukin-6(IL-6),while the expression of cytosolic P65 and IκB was significantly reduced in human umbilical vein endothelial cells(HUVECs)treated with LSS.CX3CR1 Sh-RNA was use to reveal its effect on LSS-induced inflammation.Further,specific NF-κB P65 inhibitors(PDTC)were used to reveal the downstream NF-κB P65 exclusively involved in LSS-induced inflammation in HUVECs,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.Monocyte adhesion assay and scratch test revealed LSS promotes adhesion of monocytes and migration of cells,this effect can be abrogated by CX3CR1 sh-RNA and NF-κB inhibitors.LSS is involved in the expression of adhesion moleculesand chemokines,which are important for the initiation of endothelial inflammation-related atherosclerosis.Conclusions The activation of CX3CR1/NF-κB signaling pathway induced by low shear stress in endothelial cells may lead to the future therapeutic targets of atherosclerotic inflammation.
文摘月球的低重力环境对月面浅层月壤力学特性的影响很大。利用清华大学取自吉林省靖宇县境内的火山灰岩研制出的模拟月壤（QH-E）,对GCTS公司生产的STX型动/应力路径三轴仪重新配置高精度的传感器,并采取专门的试验技术,成功实施了一系列低围压水平（3.13~25 k Pa）的三轴压缩试验。试验结果表明,在低围压水平下：模拟月壤具有显著的剪胀效应;与常规围压水平（50~150 k Pa）结果相比,同一相对密度模拟月壤的峰值摩擦角更高;相对密度越高,峰值摩擦角越大;切线模量和剪切模量均随着围压和相对密度的减小而减小;剪胀角随围压的减小和相对密度的增大而增大,且低围压水平下剪胀角对围压变化十分敏感。最后就低围压下QH-E模拟月壤与饱和砂土特性的差异,及重力场环境和施加围压的介质的影响进行了讨论。
文摘目的建立一种可调控的兔颈动脉切应力及低密度脂蛋白(low density lipoprotein,LDL)浓度极化动物模型,初步观察二者对动脉粥样硬化(artherosclerosis,AS)形成的影响。方法兔左颈总动脉施以3个狭窄度(30%、40%、50%)的硅胶管环扎手术,以右颈总动脉为假手术对照;饲喂含4种不同胆固醇浓度(0%、0.5%、1%、1.5%)饲料;彩色超声检测双侧颈总动脉血流动力学参数,计算切应力值,血管标本行病理及扫描电镜观察。结果同一狭窄度,左颈总动脉切应力随饲喂饲料所含胆固醇浓度的增加而增加;同一胆固醇浓度,左颈总动脉切应力以40%狭窄度组最低;同一样本,左颈总动脉切应力高于右颈总动脉(P<0.05)。病理切片及扫描电镜检测显示各组动物左颈总动脉均出现不同程度的AS病变,以40%狭窄度组病变更为显著。结论成功建立了可调控的兔颈总动脉切应力及LDL浓度极化模型,低切应力及LDL浓度极化促进AS的形成和发展。
