The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension
The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension
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DOI：
10.1152/ajpheart.00324.2009
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发表时间：
2009-09-01
影响因子：
4.8
通讯作者：
Tarbell, John M.
中科院分区：
文献类型：
--
作者：
Dabagh, Mahsa;Jalali, Payman;Tarbell, John M.
Dabagh M，Jalali P，Tarbell JM.低密度脂蛋白通过可变形动脉壁的转运：高血压下内皮细胞更新和内膜变形的影响。Am J Physiol Heart Circ Physiol 297：H983-H996，2009.首次发表于2009年7月10日; doi：10.1152/ajpheart.00324.2009。本文建立了主动脉壁的多层模型，考虑到内皮细胞更新率增加和内膜在高压下变形的影响，研究了高血压下低密度脂蛋白（LDL）的转运。同时，内皮、内膜、内弹性膜（IEL）和中膜的厚度和性质受跨壁压的影响。LDL大分子通过内皮上的渗漏连接进入内膜，这些渗漏连接是由死亡或分裂的细胞产生的。水分子通过细胞旁途径进入内膜，在通过糖萼后通过紧密连接的断裂以及通过渗漏连接。糖萼被建模为Brinkman多孔介质来描述与其结构相关的流体过滤。跨壁流动采用Navier-Stokes方程和Brinkman方程相结合的方法求解，LDL输运采用对流扩散方程。LDL在平滑肌细胞表面的渗透通过均匀分布在宏观均匀介质层中的均匀反应来建模。模拟是在一个轴对称的平面中心在一个泄漏的细胞。最重要的问题是，LDL穿过渗漏连接、内膜、IEL中的窗孔和中膜层的流量受到跨壁压的高度影响，这会影响内皮细胞更新率和内膜压实。本模型，第一次，没有可调的参数，是能够作出许多现实的预测，包括适当的幅度的内皮和内膜层的渗透性和所有层的水力传导率，以及它们的趋势与压力。在70和180 mmHg下，通过壁的体积通量和整个动脉壁、内皮和内皮下层的水力传导率的结果与先前的实验研究一致。
Dabagh M, Jalali P, Tarbell JM. The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension. Am J Physiol Heart Circ Physiol 297: H983-H996, 2009. First published July 10, 2009; doi: 10.1152/ajpheart.00324.2009.-A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the influences of increased endothelial cell turnover and deformation of the intima at higher pressure. Meanwhile, the thickness and properties of the endothelium, intima, internal elastic lamina (IEL), and media are affected by the transmural pressure. The LDL macromolecules enter the intima through leaky junctions over the endothelium, which are created by dying or dividing cells. Water molecules enter the intima via the paracellular pathway through breaks in tight junctions after passing the glycocalyx as well as through leaky junctions. The glycocalyx is modeled as a Brinkman porous medium to describe the fluid filtration associated with its structure. Combined Navier-Stokes and Brinkman equations are solved for the transmural flow, and the convective-diffusion equation is employed for LDL transport. The permeation of LDL over the surface of smooth muscle cells is modeled through a uniform reaction evenly distributed in the macroscopically homogeneous media layer. Simulations are performed in an axisymmetric plane centered at a leaky cell. The overriding issue addressed is that LDL fluxes across the leaky junction, the intima, fenestral pores in the IEL, and the media layer are highly affected by the transmural pressure, which affects the endothelial cell turnover rate and the compaction of intima. The present model, for the first time and with no adjustable parameters, is capable of making many realistic predictions including the proper magnitudes for the permeability of endothelium and intimal layers and the hydraulic conductivity of all layers as well as their trends with pressure. Results for the volume flux through the wall and the hydraulic conductivity of the entire arterial wall, the endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement with previous experimental studies.