Mass transport, atherogenesis, and risk.
If the local chemically-active interstitial concentration (chemical activity) of a particular atherogenic molecule (atherogen) is considered to be one of the fundamental driving forces in a system of reactions that produces an associated local atherogenic change, then the chemical activity may be used as a measure of the potential for lesion development or local "risk." A model of steady-state, combined, diffusive and convective transport of an assumed atherogen across a multilayered arterial wall was used to illustrate mechanisms by which transport processes interact with tissue barriers to determine the transmural (x axis) chemical activity distributions [a(x), mol cm-3]. The model was used to evaluate the effects of increased endothelial gap fractional area (increased endothelial permeability), elevated blood pressure, elevated serum concentration of the atherogen, internal elastica fenestration, and preexisting intimal thickening on a(x). It was found that sites along the arterial tree that are characterized by "mild" increases in endothelial gap fractional area and concomitant subjacent interstitial sieving of the atherogen developed high a(x), in some cases much higher than that (a0) of the blood, and therefore were at high risk even in the absence of other risk factors. Moreover, the risk at such sites was dramatically increased with hypertension and/or elevated serum atherogen concentration and/or preexisting intimal thickening. However, if either condition, i.e., opened endothelial intercellular junctions or subjacent interstitial sieving, was absent, these other risk factors were ineffective. Finally, the response of the model was shown to be consistent with a variety of well-known, as well as puzzling, observations suggesting that transport processes may play roles in determining both the architecture of the atherosclerotic lesion and its rate of development.
D001161:Arteriosclerosis / Q000209:etiology*; D001692:Biological Transport; D004058:Diffusion; D004727:Endothelium / Q000378:metabolism; D046911:Macromolecular Substances; D008954:Models, Biological; D012306:Risk
D046911:Macromolecular Substances