A biologically plausible model of thickening of arterial intima under shear.

Abstract

A biologically plausible model of the early thickening of the arterial Intima has been developed to interpret experimental data relating hemodynamlc shear to human Intimal morphology. The model Included many processes known or commonly believed to take place In the vascular Intima, including: smooth muscle cell migration, proliferation, metabolism, and expression of extracellular matrix; llpoproteln kinetics and binding; and monocyte chemotaxls, conversion to macrophage, and foam cell formation. Certain of these processes were allowed to be shear-dependent. The best fit to the data was obtained when smooth muscle cell accumulation was more rapid, and extracellular matrix expression proceeded more slowly where the fluid shear was relatively high and unidirectional. This result Is consistent with the earlier Inference that competing shear-dependent processes take place in the wall; It is also consistent with the notion that Intimal thickening might be part of an adaptive mechanism by which the artery maintains a favorable shear environment. (Arteriosclerosis 9:511-522, July/August 1989) I n earlier work, 1 we presented the correlations between intimal thickness and wall shear rates measured in flow-through casts of 10 human aortic bifurcations. These correlations suggested that the intima initially thickens more rapidly where shear is high or unidirectional, but ultimately reaches greater thicknesses where the shear is relatively low and oscillatory. It was shown that this behavior, more complex than had earlier been supposed, could reflect the influence of competing shear-dependent processes.A simple mathematical model of intimal thickening was developed to demonstrate that competing processes could be responsible for the experimental results; in it, intimal thickness was determined by a balance between the shear-dependent uptake and shear-dependent removal of an unspecified blood-borne substance. Here, we extend this demonstration by using a more realistic model that better reflects current understanding of the biological processes that take place in the arterial wall during the early stages of intimal thickening.This paper begins with a description of the baseline model and certain optional processes. Following a welldefined protocol, a more complex model Is then constructed by adding to the baseline model two optional processes whose inclusion significantly improves the fit of the model to the intimal thickness and hemodynamic data obtained earlier.

Effects of Coronary Heart Disease Risk Factors on Atherosclerosis of Selected Regions of the Aorta and Right Coronary Artery

“…Hypotheses explaining the localization of atherosclerotic lesions include hemodynamic stresses related to arterial geometry [1][2][3][4] ; anatomic, cellular, or biochemical variations in the arterial wall, particularly in endothelium 5 ; smooth muscle cell mutations leading to monoclonal proliferation 6 ; and infectious agents. 7 Most of the established major risk factors for coronary heart disease are associated with the extent of both fatty streaks and raised lesions in the large muscular and elastic arteries of adults 8 and also in arteries of adolescents and young adults.…”

Coagulation factors X, Xa, and protein S as potent mitogens of cultured aortic smooth muscle cells.

“…SMC replication is well documented in these models, an extensive list of cell types has been postulated to provide the mitogenic signal, and based on these studies several theories of atherogenesis in humans have been advanced (5)(6)(7)(8)(9)(10). During the early stages of atherogenesis, macrophages that adhere and infiltrate vascular endothelium are good candidates for such growth factor production as platelet-derived growth factor (PDGF) and interleukin 1 (11)(12)(13)(14).…”

B‐flow sonographic demonstration for assessing carotid atherosclerosis in young patients with heterozygous familial hypercholesterolemia

“…1,2,13,14 In our study, we found that B-flow sonography with high frame rates could visualize both the vascular hemodynamics and the interaction of blood flow with anatomical structures inside the vessel. In contrast, these fine details are often masked by the color overlay in color flow imaging.…”

“…6,14 Such hemodynamic characteristics tend to increase the residence time of circulating particles in susceptible regions and may result in shear stress-induced platelet aggregation, whereas particles are cleared rapidly from regions of relatively high wall shear stress and unidirectional laminar flow. 15,16 In addition, shear stress modulates the transcription of genes for nitric oxide synthase, platelet-derived growth factor A-and B-chain, prostacyclin, and transforming growth factor 1.…”