Mechanical stimuli play critical roles in cardiovascular diseases,in which in vivo stresses in blood vessels present a great challenge to predict.Based on the structural-thermal coupled finite element method,we propos...Mechanical stimuli play critical roles in cardiovascular diseases,in which in vivo stresses in blood vessels present a great challenge to predict.Based on the structural-thermal coupled finite element method,we propose a thermal expansion method to estimate stresses in multi-layer blood vessels under healthy and pathological conditions.The proposed method provides a relatively simple and convenient means to predict reliable in vivo mechanical stresses with accurate residual stress.The method is first verified with the opening-up process and the pressure-radius responses for single and multi-layer vessel models.It is then applied to study the stress variation in a human carotid artery at different hypertension stages and in a plaque of vascular stenosis.Our results show that specific or optimal residual stresses exist for different blood pressures,which helps form a homogeneous stress distribution across vessel walls.High elastic shear stress is identified on the shoulder of the plaque,which contributes to the tearing effect in plaque rupture.The present study indicates that the proposed numerical method is a capable and efficient in vivo stress evaluation of patient-specific blood vessels for clinical purposes.展开更多
The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseas...The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.Here,the rolling and adhesion behavior of EPCs on ECs was studied numerically.A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow.The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model.The effect of tumor necrosis factor alpha(TNF-α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally.A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs.Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiff-ness of the cell and shear rate of the flow.It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered.Experimental results demonstrate that TNF-α enhanced the expressions of VCAM,ICAM,P-selectin and E-selectin in ECs,which supports the numerical results that the rolling velocity of EPC on TNF-α treated EC substrate decreases obviously compared with its velocity on the untreated one.It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell,an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.展开更多
Acute stress concentration plays an important role in plaque rupture and may cause stroke or myocardial infarction.Quantitative evaluation of the relation between in vivo plaque stress and variations in blood pressure...Acute stress concentration plays an important role in plaque rupture and may cause stroke or myocardial infarction.Quantitative evaluation of the relation between in vivo plaque stress and variations in blood pressure and flow rates is valuable to optimize daily monitoring of the cardiovascular system for high-risk patients as well as to set a safe physical exercise intensity for better quality of life.In this study,we constructed an in vivo stress model for a human carotid bifurcation with atherosclerotic plaque,and analyzed the effects of blood pressure,flow rates,plaque stiffness,and stenosis on the elastic stress and fluid viscous stress around the plaque.According to the maximum values of the mechanical stress,we define a risk index to predict the risk level of plaque rupture under different exercise intensities.For a carotid bifurcation where the blood flow divides,the results suggest that the stenosis ratio determines the ratio of the contributions of elastic shear stress and viscous shear stress to plaque rupture.A n increase of the plaque stiffness enhances the maximum elastic shear stress in the plaque,indicating that a high-stiffness plaque is more prone to rupture for given stenosis ratio.High stress co-localization at the shoulder of plaques agrees with the region of plaque injury in clinical observations.It is demonstrated that,due to the stress-shield effect,the rupture risk of a high-stiffness plaque tends to decrease under high-stenosis conditions,suggesting the existence of a specific stenosis corresponding to the maximum risk.This study may help to complement risk stratification of vulnerable plaques in clinical practice and provides a stenosis mechanical property-specific guide for blood pressure control in cardiovascular health management.展开更多
Changes in membrane tension significantly affect the physiological functions of cells in various ways.However,directly measuring the spatial distribution of membrane tension remains an ongoing issue.In this study,an a...Changes in membrane tension significantly affect the physiological functions of cells in various ways.However,directly measuring the spatial distribution of membrane tension remains an ongoing issue.In this study,an algorithm is proposed to determine the membrane tension inversely by executing a particle-based method and searching for the minimum deformation energy based on the cell images and focal adhesions.A standard spreading cell model is established using 3D reconstructions with images from structured illumination microscopy as the reference cell shape.The membrane tension distribution,forces across focal adhesions,and profile of the spread cell are obtained using this method,until the cell deformation energy function optimization converges.Qualitative and quantitative comparisons with previous experimental results validated the reliability of this method.The results show that in the standard spreading cell model,the membrane tension decreases from the bottom to the top of the membrane.This method can be applied to predict the membrane tension distribution of cells freely spreading into different shapes,which could improve the quantitative analysis of cellular membrane tension in various studies for cell mechanics.展开更多
基金The authors would like to thank Prof.Shu Takagi and Prof.Huaxiong Huang for their instructive comments.The authors would also like to acknowledge Jianda Yang for assisting with FEM simulations.This work was supported by the National Natural Science Foundation of China(Grants 11372191,11232010,11650(Grant 91111138)the National Institute of Health(Grant 2R01DC005642-10A1).
文摘Mechanical stimuli play critical roles in cardiovascular diseases,in which in vivo stresses in blood vessels present a great challenge to predict.Based on the structural-thermal coupled finite element method,we propose a thermal expansion method to estimate stresses in multi-layer blood vessels under healthy and pathological conditions.The proposed method provides a relatively simple and convenient means to predict reliable in vivo mechanical stresses with accurate residual stress.The method is first verified with the opening-up process and the pressure-radius responses for single and multi-layer vessel models.It is then applied to study the stress variation in a human carotid artery at different hypertension stages and in a plaque of vascular stenosis.Our results show that specific or optimal residual stresses exist for different blood pressures,which helps form a homogeneous stress distribution across vessel walls.High elastic shear stress is identified on the shoulder of the plaque,which contributes to the tearing effect in plaque rupture.The present study indicates that the proposed numerical method is a capable and efficient in vivo stress evaluation of patient-specific blood vessels for clinical purposes.
基金supported by the National Natural Science Foundation of China (10732070, 11072155)Shanghai Pujiang Program (09PJ1405800)
文摘The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.Here,the rolling and adhesion behavior of EPCs on ECs was studied numerically.A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow.The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model.The effect of tumor necrosis factor alpha(TNF-α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally.A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs.Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiff-ness of the cell and shear rate of the flow.It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered.Experimental results demonstrate that TNF-α enhanced the expressions of VCAM,ICAM,P-selectin and E-selectin in ECs,which supports the numerical results that the rolling velocity of EPC on TNF-α treated EC substrate decreases obviously compared with its velocity on the untreated one.It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell,an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.
基金This work was supported by the National Key R&D Program of China(Grant 2017YFE0117100)the National Natural Science Foundation of China(Grants 11872040 and 11232010)+1 种基金the Outstanding Clinical Discipline Project of Shanghai Pudong(Grant PWYgy-2018-08)the Science and Technology Commission of Shanghai Municipality(Grant 18ZR1433900).
文摘Acute stress concentration plays an important role in plaque rupture and may cause stroke or myocardial infarction.Quantitative evaluation of the relation between in vivo plaque stress and variations in blood pressure and flow rates is valuable to optimize daily monitoring of the cardiovascular system for high-risk patients as well as to set a safe physical exercise intensity for better quality of life.In this study,we constructed an in vivo stress model for a human carotid bifurcation with atherosclerotic plaque,and analyzed the effects of blood pressure,flow rates,plaque stiffness,and stenosis on the elastic stress and fluid viscous stress around the plaque.According to the maximum values of the mechanical stress,we define a risk index to predict the risk level of plaque rupture under different exercise intensities.For a carotid bifurcation where the blood flow divides,the results suggest that the stenosis ratio determines the ratio of the contributions of elastic shear stress and viscous shear stress to plaque rupture.A n increase of the plaque stiffness enhances the maximum elastic shear stress in the plaque,indicating that a high-stiffness plaque is more prone to rupture for given stenosis ratio.High stress co-localization at the shoulder of plaques agrees with the region of plaque injury in clinical observations.It is demonstrated that,due to the stress-shield effect,the rupture risk of a high-stiffness plaque tends to decrease under high-stenosis conditions,suggesting the existence of a specific stenosis corresponding to the maximum risk.This study may help to complement risk stratification of vulnerable plaques in clinical practice and provides a stenosis mechanical property-specific guide for blood pressure control in cardiovascular health management.
基金supported by the National Key Research and Development Program of China (Grant No. 2017YFE0117100)the National Natural Science Foundation of China (Grant Nos. 11872040, and 12072198)+1 种基金the China Scholarship Council for Joint Ph.D. Program (Grant No.201206230004)funding from the Mechanobiology Institute Seed Grant and the Ministry of Education’s Academic Research Fund Tier 1 (Grant No. R-397-000-247-112)
文摘Changes in membrane tension significantly affect the physiological functions of cells in various ways.However,directly measuring the spatial distribution of membrane tension remains an ongoing issue.In this study,an algorithm is proposed to determine the membrane tension inversely by executing a particle-based method and searching for the minimum deformation energy based on the cell images and focal adhesions.A standard spreading cell model is established using 3D reconstructions with images from structured illumination microscopy as the reference cell shape.The membrane tension distribution,forces across focal adhesions,and profile of the spread cell are obtained using this method,until the cell deformation energy function optimization converges.Qualitative and quantitative comparisons with previous experimental results validated the reliability of this method.The results show that in the standard spreading cell model,the membrane tension decreases from the bottom to the top of the membrane.This method can be applied to predict the membrane tension distribution of cells freely spreading into different shapes,which could improve the quantitative analysis of cellular membrane tension in various studies for cell mechanics.