Huang Y, Rumschitzki D, Chien S, Weinbaum S
Department of Mechanical Engineering, City College, City University of New York, NY 10031.
J Biomech Eng. 1994 Nov;116(4):430-45. doi: 10.1115/1.2895794.
A new model is presented for the growth of cellular level macromolecular leakage spots in the arterial intima. The theoretical approach differs from the recent study by Yuan et al. [19] in that it directly models and calculates the intimal transport parameters based on Frank and Fogelman's [22] ultrastructural observations of the extracellular subendothelial proteoglycan matrix that their rapid freeze etching technique preserves (see Addendum). Using a heterogeneous fiber matrix theory, which includes proteoglycan and collagen components, the model predicts that the Darcy permeability Kp and macromolecular diffusivity D of the subendothelial intima is two orders of magnitude larger than the corresponding values measured in the media, and supports the observations in Lark et al. [24] that the proteoglycan structure of the intima differs greatly from that of the media. Numerical results show that convection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region of roughly 200 microns diameter surrounding the leaky cleft. The predictions of the new model for the early-time spread of the advancing convective-diffusive front from the leakage spots in the intima are in close agreement with our experimental measurements for the growth of HRP spots in [20]. The regions of high concentration surrounding the leaky cell, however, are much more limited and cover an area that is typically equivalent to 20 cells. This prediction is consistent with the recent measurements of Truskey et al. for LDL spot size in rabbit aorta [21] and the hypothesis advanced in [19] that there is a colocalization of subendothelial liposome growth and cellular level leakage. Finally, comparison of predicted and experimentally-measured average LDL concentration in leakage spots strongly suggests that there is significant local molecular sieving at the interface between the fenestral openings in the internal elastic lamina and the media.
本文提出了一种新的模型，用于描述动脉内膜中细胞水平大分子渗漏点的生长情况。该理论方法与Yuan等人[19]最近的研究不同，它基于Frank和Fogelman[22]利用快速冷冻蚀刻技术保存的细胞外内皮下蛋白聚糖基质的超微结构观察结果，直接对内膜传输参数进行建模和计算（见附录）。该模型使用包含蛋白聚糖和胶原蛋白成分的非均质纤维基质理论，预测内皮下内膜的达西渗透率Kp和大分子扩散系数D比在中膜中测得的相应值大两个数量级，并支持Lark等人[24]的观察结果，即内膜的蛋白聚糖结构与中膜有很大差异。数值结果表明，在内膜中围绕渗漏裂隙直径约200微米的大片区域内，平行于内皮的对流是大分子的一种非常重要的传输机制。新模型对内膜中渗漏点处对流扩散前沿早期扩展的预测与我们在[20]中对HRP点生长的实验测量结果非常吻合。然而，渗漏细胞周围的高浓度区域要有限得多，覆盖的面积通常相当于20个细胞。这一预测与Truskey等人最近对兔主动脉中LDL斑点大小的测量结果[21]以及[19]中提出的内皮下脂质体生长与细胞水平渗漏共定位的假设一致。最后，对渗漏点处预测的和实验测量的平均LDL浓度进行比较，强烈表明在内弹性膜的窗孔与中膜之间的界面处存在显著的局部分子筛分。
