目的研究不同血流切应力(fluid shear stress, FSS)对内皮细胞平面细胞极性通路(planar cell polarity, PCP)的调节作用,进一步探讨FSS、PCP信号通路以及纤毛发生之间的关系。方法建立可调控FSS的流体动力学细胞培养模型,qPCR以及免疫...目的研究不同血流切应力(fluid shear stress, FSS)对内皮细胞平面细胞极性通路(planar cell polarity, PCP)的调节作用,进一步探讨FSS、PCP信号通路以及纤毛发生之间的关系。方法建立可调控FSS的流体动力学细胞培养模型,qPCR以及免疫荧光检测不同FSS作用下PCP信号通路核心蛋白Dvl2及纤毛装配蛋白IFT88的mRNA表达与细胞定位以及两者的共定位,Western bolt (WB)检测不同FSS作用18 h时Dvl2蛋白表达。结果 qPCR结果显示,与1.5 Pa比较,Dvl2 mRNA的表达量在0.1 Pa FSS作用6 h和18 h时均升高(P<0.05)、12 h时显著升高(P<0.01);IFT88 mRNA表达量在0.1 Pa FSS作用18 h时显著升高(P<0.01)。WB结果显示,与0 h比较,Dvl2蛋白的表达在0.1 Pa FSS作用18 h时升高(P<0.05),在1.5 Pa FSS作用18 h时显著降低(P<0.05);与1.5 Pa FSS比较,Dvl2蛋白的表达在0.1 Pa FSS作用18 h时升高(P<0.05)。免疫荧光结果显示,Dvl2蛋白阳性表达随FSS作用时间的增加增多,且逐渐聚集于细胞核周边一点;IFT88蛋白阳性表达在0.1 Pa FSS作用下逐渐由细胞核向细胞质转移并聚集为一点,1.5 Pa FSS作用下逐渐减少且解聚;蛋白Dvl2、IFT88在0.1 Pa FSS作用下均定位于细胞的同一位置,在1.5 Pa FSS作用18 h内均定位于细胞的同一位置,18 h后由于蛋白IFT88发生解聚,未观察到共定位。结论层流FSS作用能够抑制PCP信号通路的转导并阻碍纤毛发生,低FSS促进其转导,且PCP信号通路可能通过Dvl2调控FSS诱导的初级纤毛发生。展开更多
Non-Newtonian fluid model for blood flow through a tapered artery with a stenosis and variable viscosity by modeling blood as Jeffrey fluid has been studied in this paper. The Jeffrey fluid has two parameters, the rel...Non-Newtonian fluid model for blood flow through a tapered artery with a stenosis and variable viscosity by modeling blood as Jeffrey fluid has been studied in this paper. The Jeffrey fluid has two parameters, the relaxation time A1 and retardation time A2. The governing equations are simplified using the case of mild stenosis. Perturbation method is used to solve the resulting equations. The effects of non-Newtonian nature of blood on velocity profile, temperature profile, wall shear stress, shearing stress at the stenotsis throat and impedance of the artery are discussed. The results for Newtonian fluid are obtained as special case from this model.展开更多
Objective： To determine the effect of antiparallel phosphorothioate triplex-forming oligonucleotide （apsTFO）, which was designed according to shear stress response element （SSRE） in tissue factor （TF） gene prom...Objective： To determine the effect of antiparallel phosphorothioate triplex-forming oligonucleotide （apsTFO）, which was designed according to shear stress response element （SSRE） in tissue factor （TF） gene promoter region, on the expression of endothelial TF in carotid artery stenosis rats. Methods： Rat model of severe carotid artery stenosis were inflicted by silica gel tube ligation. Half an hour before the model infliction, GT20-apsTFO, GT20-psTFO and GT21-apsTFO labeled with green fluorescence （FITC） were injected into the vena caudalis of rat at a dose of 0.5 mg/kg. Half an hour, 4 or 9 h after the ligation, the distribution of TFO in the common carotid artery, the liver and the kidney was detected with aid of fluorescence microscopy. And the mRNA and protein expressions of TF, Egr-1 and Spl in the above-mentioned organs were determined with in situ hybridization and immunohistochemical assay respectively in 6 h after the model establishment, and the results were analyzed with an image analysis system. Results： Only in 1 h after TFO injection, fluorescent granules appeared in the liver, the kidney and the vascular wall and lumen of carotid artery, and then in 4.5 h, they still deposited in above sites except the vascular lumen. GT20-apsTFO and GT21-apsTFO significant down-regulated the mRNA and protein expressions of TF compared to the rats without treatment （P〈0.05）, and the former apsTFO had a more stronger effect than the later （P〈0.05）. GT20-psTFO had no such effect （P〉0.05）. The 3 TFOs had no inhibition on the mRNA and protein expressions of Egr-1 and Spl. Conclusion： Pretreated apsTFO can partly come into the vascular endothelial cells, and inhibit TF expression induced by shear stress, but had no effect on Egr-1 and Spl gene expressions.展开更多
Pulsatile blood flows in curved atherosclerotic arteries are studied by computer simulations. Computations are carried out with various values of physiological parameters to examine the effects of flow parameters on t...Pulsatile blood flows in curved atherosclerotic arteries are studied by computer simulations. Computations are carried out with various values of physiological parameters to examine the effects of flow parameters on the disturbed flow patterns downstream of a curved artery with a stenosis at the inner wall. The numerical results indicate a strong dependence of flow pattern on the blood viscosity and inlet flow rate, while the influence of the inlet flow profile to the flow pattern in downstream is negligible.展开更多
The Chinese traditional medical massage has been used as a natural therapy to eliminate some diseases. Here, the effect of the rolling massage frequency to the blood flow in the blood vessels under the rolling massage...The Chinese traditional medical massage has been used as a natural therapy to eliminate some diseases. Here, the effect of the rolling massage frequency to the blood flow in the blood vessels under the rolling massage manipulation is studied by the lattice Boltzmann simulation. The simulation results show that when the frequency is smaller than or comparable to the pulsatile frequency of the blood flow, the effect on the blood flux by the rolling massage is small. 011 the contrast, if the frequency is twice or more times of the pulsatile frequency of the blood flow, the blood flux is greatly enhanced and increases linearly with respect to the frequency. Similar behavior has also been observed on the shear stress on the blood vessel walls. The result is helpful for understanding that the rolling massage has the function of promoting the blood circulation and removing the blood stasis.展开更多
The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensu...The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensus that the stent implant may change the artery wall shear stress distribution and hence lead to the restenosis process. Computational fluid dynamics （CFD） has been widely used to analyze hemodynamics in stented arteries. In this paper, two CFD models （the axisymmetric model and the 3-D stent model） were developed to investigate the effects of strut geometry and blood rheology on the intra-stent hemodynamics. The velocity profile, flow recirculation, and wall shear stress distribution of various stent strut geometries were studied. Results show strong correlations between the intra-stent hemodynamics and strut geometry. The intra-stent blood flow is very sensitive to the strut height and fillet size. A round strut with a large fillet size shows 36% and 34% reductions in key parameters evaluating the restenosis risk for the axisymmetric model and the 3-D stent model, respectively. This suggests that electrochemical polishing, a surface-improving process during stent manufacturing, strongly influences the hemodynamic behavior in stented arteries and should be controlled precisely in order to achieve the best clinical outcome. Rheological effects on the wall shear stress are minor in both axisymmetric and 3-D stent models for the vessel diameter of 4 mm, with Newtonian flow simulation tending to give more conservative estimates ofrestenosis risk. Therefore, it is reasonable to simulate the blood flow as a Newtonian flow in stented arteries using the simpler axisymmetric model. These findings will provide great insights for stent design optimization for potential restenosis improvement.展开更多
Circulating leukocytes in trafficking to the inflammatory sites, will be first tether to, and then roll on the vascular surface. This event is mediated through specific interaction of P-selectin and P-selectin glycopr...Circulating leukocytes in trafficking to the inflammatory sites, will be first tether to, and then roll on the vascular surface. This event is mediated through specific interaction of P-selectin and P-selectin glycoprotein ligand-1 （PSGL-1）, and regulated by hemodynamics. Poor data were reported in understanding P-selectin-mediated rolling. With the flow chamber technique, we herein observed HL-60 cell rolling on P-selectin with or without 3% Ficoll at various wall shear stresses from 0.05 to 0.4 dyn/cm：. The results demonstrated that force rather than transport regulated the rolling, similar to rolling on L- and E-selectin. The rolling was accelerated quickly by an increasing force below the optimal shear threshold of 0.15 dyn/cm2 first and then followed by a slowly decelerating phase starting at the optimum, showing a catch-slip transition and serving as a mechanism for the rolling. The catch-slip transition was completely reflected to the tether lifetime and other rolling parameters, such as the mean and fractional stop time. The narrow catch bond regime stabilized the rolling quickly, through steeply increasing frac- tional stop time to a plateau of about 0.85. Data presented here suggest that the low shear stress threshold serves as a mecha- nism for most cell rolling events through P-selectin.展开更多
In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteristics is analyzed, assuming the flow is steady a...In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteristics is analyzed, assuming the flow is steady and blood is treated as Williamson fluid. Per- turbation solutions have been evaluated for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different type of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different parameters of interest.展开更多
In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteris- tics is analyzed, assuming the flow is steady...In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteris- tics is analyzed, assuming the flow is steady and blood is treated as Williamson fluid. The effects of mixed convection heat and mass transfer are also carried out. Perturbation solutions have been calculated for velocity, temperature, concentration, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different types of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different parameters of interest. Streamlines have been plotted at the end of the paper.展开更多
In the present paper, we have studied the blood flow through tapered artery with a stenosis. The non-Newtonian nature of blood in small arteries is analyzed mathematically by considering the blood as Phan-Thien-Tanner...In the present paper, we have studied the blood flow through tapered artery with a stenosis. The non-Newtonian nature of blood in small arteries is analyzed mathematically by considering the blood as Phan-Thien-Tanner fluid. The representation for the blood flow is through an axially non-symmetrical but radially symmetric stenosis. Symmetry of the distribution of the wall shearing stress and resistive impedance and their growth with the developing stenosis is another important feature of our analysis. Exact solutions have been evaluated for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different type of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different narameters of interest.展开更多
文摘目的研究不同血流切应力(fluid shear stress, FSS)对内皮细胞平面细胞极性通路(planar cell polarity, PCP)的调节作用,进一步探讨FSS、PCP信号通路以及纤毛发生之间的关系。方法建立可调控FSS的流体动力学细胞培养模型,qPCR以及免疫荧光检测不同FSS作用下PCP信号通路核心蛋白Dvl2及纤毛装配蛋白IFT88的mRNA表达与细胞定位以及两者的共定位,Western bolt (WB)检测不同FSS作用18 h时Dvl2蛋白表达。结果 qPCR结果显示,与1.5 Pa比较,Dvl2 mRNA的表达量在0.1 Pa FSS作用6 h和18 h时均升高(P<0.05)、12 h时显著升高(P<0.01);IFT88 mRNA表达量在0.1 Pa FSS作用18 h时显著升高(P<0.01)。WB结果显示,与0 h比较,Dvl2蛋白的表达在0.1 Pa FSS作用18 h时升高(P<0.05),在1.5 Pa FSS作用18 h时显著降低(P<0.05);与1.5 Pa FSS比较,Dvl2蛋白的表达在0.1 Pa FSS作用18 h时升高(P<0.05)。免疫荧光结果显示,Dvl2蛋白阳性表达随FSS作用时间的增加增多,且逐渐聚集于细胞核周边一点;IFT88蛋白阳性表达在0.1 Pa FSS作用下逐渐由细胞核向细胞质转移并聚集为一点,1.5 Pa FSS作用下逐渐减少且解聚;蛋白Dvl2、IFT88在0.1 Pa FSS作用下均定位于细胞的同一位置,在1.5 Pa FSS作用18 h内均定位于细胞的同一位置,18 h后由于蛋白IFT88发生解聚,未观察到共定位。结论层流FSS作用能够抑制PCP信号通路的转导并阻碍纤毛发生,低FSS促进其转导,且PCP信号通路可能通过Dvl2调控FSS诱导的初级纤毛发生。
文摘Non-Newtonian fluid model for blood flow through a tapered artery with a stenosis and variable viscosity by modeling blood as Jeffrey fluid has been studied in this paper. The Jeffrey fluid has two parameters, the relaxation time A1 and retardation time A2. The governing equations are simplified using the case of mild stenosis. Perturbation method is used to solve the resulting equations. The effects of non-Newtonian nature of blood on velocity profile, temperature profile, wall shear stress, shearing stress at the stenotsis throat and impedance of the artery are discussed. The results for Newtonian fluid are obtained as special case from this model.
基金the National Natural Science Foundation of China (39970269)
文摘Objective： To determine the effect of antiparallel phosphorothioate triplex-forming oligonucleotide （apsTFO）, which was designed according to shear stress response element （SSRE） in tissue factor （TF） gene promoter region, on the expression of endothelial TF in carotid artery stenosis rats. Methods： Rat model of severe carotid artery stenosis were inflicted by silica gel tube ligation. Half an hour before the model infliction, GT20-apsTFO, GT20-psTFO and GT21-apsTFO labeled with green fluorescence （FITC） were injected into the vena caudalis of rat at a dose of 0.5 mg/kg. Half an hour, 4 or 9 h after the ligation, the distribution of TFO in the common carotid artery, the liver and the kidney was detected with aid of fluorescence microscopy. And the mRNA and protein expressions of TF, Egr-1 and Spl in the above-mentioned organs were determined with in situ hybridization and immunohistochemical assay respectively in 6 h after the model establishment, and the results were analyzed with an image analysis system. Results： Only in 1 h after TFO injection, fluorescent granules appeared in the liver, the kidney and the vascular wall and lumen of carotid artery, and then in 4.5 h, they still deposited in above sites except the vascular lumen. GT20-apsTFO and GT21-apsTFO significant down-regulated the mRNA and protein expressions of TF compared to the rats without treatment （P〈0.05）, and the former apsTFO had a more stronger effect than the later （P〈0.05）. GT20-psTFO had no such effect （P〉0.05）. The 3 TFOs had no inhibition on the mRNA and protein expressions of Egr-1 and Spl. Conclusion： Pretreated apsTFO can partly come into the vascular endothelial cells, and inhibit TF expression induced by shear stress, but had no effect on Egr-1 and Spl gene expressions.
文摘Pulsatile blood flows in curved atherosclerotic arteries are studied by computer simulations. Computations are carried out with various values of physiological parameters to examine the effects of flow parameters on the disturbed flow patterns downstream of a curved artery with a stenosis at the inner wall. The numerical results indicate a strong dependence of flow pattern on the blood viscosity and inlet flow rate, while the influence of the inlet flow profile to the flow pattern in downstream is negligible.
基金supported by the National Fundamental Research Program of China under Grant No.2006CB708612Zhejiang Funding Scheme to Young College Teachers
文摘The Chinese traditional medical massage has been used as a natural therapy to eliminate some diseases. Here, the effect of the rolling massage frequency to the blood flow in the blood vessels under the rolling massage manipulation is studied by the lattice Boltzmann simulation. The simulation results show that when the frequency is smaller than or comparable to the pulsatile frequency of the blood flow, the effect on the blood flux by the rolling massage is small. 011 the contrast, if the frequency is twice or more times of the pulsatile frequency of the blood flow, the blood flux is greatly enhanced and increases linearly with respect to the frequency. Similar behavior has also been observed on the shear stress on the blood vessel walls. The result is helpful for understanding that the rolling massage has the function of promoting the blood circulation and removing the blood stasis.
文摘The stent was a major breakthrough in the treatment of atherosclerotic vascular disease. The permanent vascular implant of a stent, however, changes the intra-stent blood flow hemodynamics. There is a growing consensus that the stent implant may change the artery wall shear stress distribution and hence lead to the restenosis process. Computational fluid dynamics （CFD） has been widely used to analyze hemodynamics in stented arteries. In this paper, two CFD models （the axisymmetric model and the 3-D stent model） were developed to investigate the effects of strut geometry and blood rheology on the intra-stent hemodynamics. The velocity profile, flow recirculation, and wall shear stress distribution of various stent strut geometries were studied. Results show strong correlations between the intra-stent hemodynamics and strut geometry. The intra-stent blood flow is very sensitive to the strut height and fillet size. A round strut with a large fillet size shows 36% and 34% reductions in key parameters evaluating the restenosis risk for the axisymmetric model and the 3-D stent model, respectively. This suggests that electrochemical polishing, a surface-improving process during stent manufacturing, strongly influences the hemodynamic behavior in stented arteries and should be controlled precisely in order to achieve the best clinical outcome. Rheological effects on the wall shear stress are minor in both axisymmetric and 3-D stent models for the vessel diameter of 4 mm, with Newtonian flow simulation tending to give more conservative estimates ofrestenosis risk. Therefore, it is reasonable to simulate the blood flow as a Newtonian flow in stented arteries using the simpler axisymmetric model. These findings will provide great insights for stent design optimization for potential restenosis improvement.
基金supported by the National Natural Science Foundation of China(Grant Nos.11272125,11072080,31170887 and 31200705)Guangdong Natural Science Foundation(Grant No.S2011010005451)Specialized Research Fund for the Doctoral Program of Higher Education(Grant No.20110172110030)
文摘Circulating leukocytes in trafficking to the inflammatory sites, will be first tether to, and then roll on the vascular surface. This event is mediated through specific interaction of P-selectin and P-selectin glycoprotein ligand-1 （PSGL-1）, and regulated by hemodynamics. Poor data were reported in understanding P-selectin-mediated rolling. With the flow chamber technique, we herein observed HL-60 cell rolling on P-selectin with or without 3% Ficoll at various wall shear stresses from 0.05 to 0.4 dyn/cm：. The results demonstrated that force rather than transport regulated the rolling, similar to rolling on L- and E-selectin. The rolling was accelerated quickly by an increasing force below the optimal shear threshold of 0.15 dyn/cm2 first and then followed by a slowly decelerating phase starting at the optimum, showing a catch-slip transition and serving as a mechanism for the rolling. The catch-slip transition was completely reflected to the tether lifetime and other rolling parameters, such as the mean and fractional stop time. The narrow catch bond regime stabilized the rolling quickly, through steeply increasing frac- tional stop time to a plateau of about 0.85. Data presented here suggest that the low shear stress threshold serves as a mecha- nism for most cell rolling events through P-selectin.
文摘In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteristics is analyzed, assuming the flow is steady and blood is treated as Williamson fluid. Per- turbation solutions have been evaluated for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different type of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different parameters of interest.
文摘In this paper, the blood flow through a tapered artery with a stenosis by considering axially non-symmetric but radially symmetric mild stenosis on blood flow characteris- tics is analyzed, assuming the flow is steady and blood is treated as Williamson fluid. The effects of mixed convection heat and mass transfer are also carried out. Perturbation solutions have been calculated for velocity, temperature, concentration, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different types of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different parameters of interest. Streamlines have been plotted at the end of the paper.
文摘In the present paper, we have studied the blood flow through tapered artery with a stenosis. The non-Newtonian nature of blood in small arteries is analyzed mathematically by considering the blood as Phan-Thien-Tanner fluid. The representation for the blood flow is through an axially non-symmetrical but radially symmetric stenosis. Symmetry of the distribution of the wall shearing stress and resistive impedance and their growth with the developing stenosis is another important feature of our analysis. Exact solutions have been evaluated for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different type of tapered arteries （i.e. converging tapering, diverging tapering, non-tapered artery） have been examined for different narameters of interest.
