A FIBER-MATRIX MODEL FOR THE GROWTH OF MACROMOLECULAR LEAKAGE SPOTS IN THE ARTERIAL INTIMA

A new model is presented for the growth of cellular level macromolecul ar leakage spots in the arterial intima. The theoretical approach diff ers from the recent study by Yuan et al. [19] in that if directly mode ls and calculates the intimal transport parameters based on Frank and Fogelman's [22] ultrastructural observations of the extracellular sube ndothelial proteoglycan matrix that their rapid freeze etching techniq ue preserves (see Addendum). Using a heterogeneous fiber matrix theory , which includes proteoglycan and collagen components, the model predi cts that the Darcy permeability K-p and macromolecular diffusivity D o f the subendothelial intima is two orders of magnitude larger than the corresponding values measured in the media, and supports the observat ions in Lark et al. [24] that the proteoglycan structure of the intima differs greatly from that of the media. Numerical results show that c onvection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region of roughl y 200 mu m diameter surrounding the leaky cleft. The predictions of th e new model for the early-time spread of the advancing convective-diff usive front from the leakage spots in the intima are in close agreemen t,vith our experimental measurements for the growth of HRP spots in [2 0]. The regions of high concentration surrounding the leaky cell, howe ver, are much more limited and cover an area that is typically equival ent to 20 cells. This prediction is consistent with the recent measure ments of Truskey et al. for LDL spot size in rabbit aorta [21] and the hypothesis advanced in [19] that there is a colocalization of subendo thelial liposome growth and cellular level leakage. Finally, compariso n of predicted and experimentally-measured average LDL concentration i n leakage spots strongly suggests that there is significant local mole cular sieving at the interface between the fenestral openings in the i nternal elastic lamina and the media.