A Mathematical Model for ATP-Mediated Calcium Dynamics in Vascular Endothelial Cells Induced by Fluid Shear Stress
-
摘要: 考虑剪应力诱导血管内皮细胞钙离子内流主要取决于经由三磷酸腺苷（ATP）门控离子通道P2X4的钙离子内流这一实验事实，提出一个修正的剪应力诱导钙离子内流模型，认为钙离子内流量不仅取决于细胞膜内外钙离子浓度差，而且受细胞表面ATP浓度调节A·D2同时利用文献中公布的实验结果，建立了一个新的静态ATP分泌模型，并将其整合到修正后的钙离子内流模型中，建立了一个描述动脉内皮细胞内非线性钙离子动力学系统．求解整合后动力学系统的控制方程，可获得内皮细胞在剪应力作用下受ATP调节的钙离子响应．结果表明，与文献中其他模型比较，改进后的模型模拟的结果能更真实地反映实验事实．Abstract: In consideration of the mechanism for shear-stress-induced calcium influx via ATP(adeno-sine triphosphate)-gated ion channel P2X4 in vascular endothelial cells,a modified model was proposed to describe the shea-rstress-induced calcium influx,which is considered to be effected not only by the calcium gradient across the cell membrane but also by the extracellular ATP concentration on the cell surface.Meanwhile a new static ATP release model was constructed with published experimental data.Combining the modified intracellular calcium dynamics model with the new ATP release model,a nonlinear calcium dynamic system in vascular endothelial cells was establshed.The ATP- mediated calcium response in vascular endothelial cells subjected to shear stress was analyzed by solving the governing equations of the integrated dynamic system.The numerical results show that the shea-rstress-induced calcium response predicted by the proposed model is more consistent with the experimental observations than that predicted by the existing models in the literature.
-
Key words:
- shear stress /
- mechanotransduction /
- vascular endothelial cells /
- ATP(adenosine triphosphate) /
- calcium /
- static model /
- dynamic model
-
[1] Ando J, Komatsuda T, Kamiya A. Cytoplasmic calcium responses to fluid shear stress in cultured vascular endothelial cells[J].In Vitro Cell Dev Biol，1988，24(9):871-877. doi: 10.1007/BF02623896 [2] Davies P F. Flow-mediated endothelial mechanotransduction[J].Physiol Rev，1995，75(3):519-560. [3] Dull R O， Davies P F. Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells[J].Am J Physiol，1991，261(1Pt2):H149-H156. [4] Mo M, Eskin S G,Schilling W P. Flow-induced changes in calcium signaling of vascular endothelial cells:effects of shear stress and ATP[J].Am J Physiol，1991，260(5Pt2): H1698-H1707. [5] Yamamoto K, Sokabe T, Ohura N,et al.Endogenously released ATP mediates shear-stress-induced Ca2+ influx into pulmonary artery endothelial cells[J].Am J Physiol，2003，285(2):H793-H803. [6] Wiesner T F, Berk B C,Nerem R M.A mathematical model of the cytosolic-free calcium response in endothelial cells to fluid shear stress[J].PNAS，1997，94(8):3726-3731. doi: 10.1073/pnas.94.8.3726 [7] Shi X M, Zheng Y F, Liu Z R,et al.A model of calcium signaling and degranulation dynamics induced by laser irradiation in mast cells[J].Chinese Science Bulletin,2008,53(15):2315-2325. doi: 10.1007/s11434-008-0255-z [8] John K, Barakat A I. Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow-induced ATP release[J].Ann Biomed Eng，2001，29(9):740-751. doi: 10.1114/1.1397792 [9] Plank M J, Wall D J N, David T. Atherosclerosis and calcium signaling in endothelial cells[J].Prog Biophys Mol Biol，2006，91(3): 287-313. doi: 10.1016/j.pbiomolbio.2005.07.005 [10] Kumar V, Pandey R N,Upadhyay S N. A closed form solution of convective mass transfer model for intracellular calcium response of endothelial cells[J].Mathematical Problems in Engineering，1998，4(5):437-459. doi: 10.1155/S1024123X9800091X [11] Qin K R, Xiang C, Xu Z,et al.Dynamic modeling for shear stress induced ATP release from vascular endothelial cells[J].Biomech Model Mechanobiol,2008,7(5):345-353. doi: 10.1007/s10237-007-0088-8 -
计量
- 文章访问数: 2783
- HTML全文浏览量: 168
- PDF下载量: 762
- 被引次数: 0
下载:
渝公网安备50010802005915号