A new dynamic model for cell-deformation-induced adenosine triphosphate （ATP） release from vascular endothelial cells （VECs） is proposed in this paper to quantify the relationship between the ATP concentration at ...A new dynamic model for cell-deformation-induced adenosine triphosphate （ATP） release from vascular endothelial cells （VECs） is proposed in this paper to quantify the relationship between the ATP concentration at the surface of VECs and blood flow-induced shear stress. The simulation results demonstrate that ATP concentration at the surface of VECs predicted by the proposed new dynamic model is more consistent with the experimental observations than those by the existing static and dynamic models. Furthermore, it is the first time that a proportional-integral-derivative （PID） feedback controller is applied to modulate extracellular ATP concentration. Three types of desired ATP concentration profiles including constant, square wave and sinusoid are obtained by regulating the wall shear stress under this PID control. The systematic methodology utilized in this paper to model and control ATP release from VECs via adjusting external stimulus opens up a new scenario where quantitative investigations into the underlying mechanisms for many biochemical phenomena can be carded out for the sake of controlling specific cellular events.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
In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stres...In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stress-induced Ca^2＋ influx. It is affected both by the Ca^2＋ gradient across the cell membrane and extracellular ATP concentration on the cell surface. Meanwhile, a new static ATP release model is constructed by using published experimental data. Combining the modified intracellular calcium dynamics model with the new ATP release model, we establish a nonlinear Ca^2＋ dynamic system in vascular endothelial cells. The ATP-mediated calcium response in vascular endothelial cells subjected to shear stresses is analyzed by solving the governing equations of the integrated dynamic system. Numerical results show that the shear-stress-induced calcium response predicted by the proposed model is more consistent with the experimental observations than that predicted by existing models.展开更多
Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation ...Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation of stem cells via serious signaling pathways.The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis.In normal tissues,blood flow directly affects the microenvironment of vascular endothelial cells(ECs);in pathological status,the abnormal interactions between blood flow and vessels contribute to the injury of vessels.Next,the altered mechanical forces are transduced into cells by mechanosensors to trigger the reformation of vessels.This process occurs when signaling pathways related to EC differentiation are initiated.Hence,a deep understanding of the responses of stem cells to mechanical stresses and the underlying mechanisms involved in this process is essential for clinical translation.In this the review,we provide an overview of the role of stem cells in vascular repair,outline the performance of stem cells under the mechanical stress stimulation,and describe the related signaling pathways.展开更多
目的在体研究切应力诱导内皮细胞TF基因表达变化规律及其机制。方法54只SD大鼠随机分为对照组和颈动脉狭窄组,狭窄组有又分为0.5、1、3、6、12 h、1、3、7 d 8个时相点,套扎法建立左颈总动脉狭窄模型,术后不同时相点用原位杂交和免疫组...目的在体研究切应力诱导内皮细胞TF基因表达变化规律及其机制。方法54只SD大鼠随机分为对照组和颈动脉狭窄组,狭窄组有又分为0.5、1、3、6、12 h、1、3、7 d 8个时相点,套扎法建立左颈总动脉狭窄模型,术后不同时相点用原位杂交和免疫组化法检测TF、Egr、Sp-1的mRNA和蛋白,用图像分析系统测定内膜平均灰度,进行统计学分析。结果正常对照组内皮细胞TF、Egr-1、Sp-1的mRNA和蛋白弱表达,狭窄30 m in后,内皮细胞胞浆组织因子基因mRNA转录和蛋白合成升高,与对照组比较均有显著性差异(P<0.05)。内皮细胞胞核和胞浆的Sp-1和Egr-1基因mRNA转录和蛋白合成均有显著性增加(P<0.05),但以Egr-1增加更显著(P<0.05),其变化趋势与组织因子基因mRNA转录、组织因子基因蛋白合成的变化趋势相同。TF mRNA和蛋白6 h达到峰值,Egr-1 mRNA和蛋白3 h达到峰值,Sp-1 mRNA和蛋白1 h达到峰值,与邻近组比较差异显著(P<0.05)。结论切应力是内皮细胞组织因子基因表达上调的触发因素之一,切应力激活TF与转录因子Egr-1和Sp-1介导有关。展开更多
基金supported by NUS Academic Research Fund (R-263-000-483-112)
文摘A new dynamic model for cell-deformation-induced adenosine triphosphate （ATP） release from vascular endothelial cells （VECs） is proposed in this paper to quantify the relationship between the ATP concentration at the surface of VECs and blood flow-induced shear stress. The simulation results demonstrate that ATP concentration at the surface of VECs predicted by the proposed new dynamic model is more consistent with the experimental observations than those by the existing static and dynamic models. Furthermore, it is the first time that a proportional-integral-derivative （PID） feedback controller is applied to modulate extracellular ATP concentration. Three types of desired ATP concentration profiles including constant, square wave and sinusoid are obtained by regulating the wall shear stress under this PID control. The systematic methodology utilized in this paper to model and control ATP release from VECs via adjusting external stimulus opens up a new scenario where quantitative investigations into the underlying mechanisms for many biochemical phenomena can be carded out for the sake of controlling specific cellular events.
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the National Natural Science Foundation of China(No.10472027) the NUS Academic Research Fund(No.R-263-000-483-112)
文摘In consideration of the mechanism for shear-stress-induced Ca^2＋ influx via ATP（adenosine triphosphate）-gated ion channel P2X4 in vascular endothelial cells, a modified model is proposed to describe the shear-stress-induced Ca^2＋ influx. It is affected both by the Ca^2＋ gradient across the cell membrane and extracellular ATP concentration on the cell surface. Meanwhile, a new static ATP release model is constructed by using published experimental data. Combining the modified intracellular calcium dynamics model with the new ATP release model, we establish a nonlinear Ca^2＋ dynamic system in vascular endothelial cells. The ATP-mediated calcium response in vascular endothelial cells subjected to shear stresses is analyzed by solving the governing equations of the integrated dynamic system. Numerical results show that the shear-stress-induced calcium response predicted by the proposed model is more consistent with the experimental observations than that predicted by existing models.
基金Supported by the National Natural Science Foundation of China,No.11672197 and No.81702171the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen,No.201806081018272960
文摘Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation of stem cells via serious signaling pathways.The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis.In normal tissues,blood flow directly affects the microenvironment of vascular endothelial cells(ECs);in pathological status,the abnormal interactions between blood flow and vessels contribute to the injury of vessels.Next,the altered mechanical forces are transduced into cells by mechanosensors to trigger the reformation of vessels.This process occurs when signaling pathways related to EC differentiation are initiated.Hence,a deep understanding of the responses of stem cells to mechanical stresses and the underlying mechanisms involved in this process is essential for clinical translation.In this the review,we provide an overview of the role of stem cells in vascular repair,outline the performance of stem cells under the mechanical stress stimulation,and describe the related signaling pathways.
