Transport of ¹⁴ C-4-Cholesterol between Serum and Wall in the Perfused Dog Common Carotid Artery

Abstract

The transport of certain materials between the blood and the wall in arteries appears to be dependent on wall shear rate with shear rate-enhancing flux; however, the mechanism is unclear. If the transport is diffusional, it must involve three steps: diffusion across a boundary layer, uptake at the blood-wall interface, and transport within the wall. If the first step is rate controlling, if wall shear rate is spatially uniform, and if a diffusion boundary layer commences upstream at the junction between the vessel and an impermeable tube, then flux will be proportional to the cube root of wall shear rate divided by distance and will depend on the species diffusion coefficient. A dog's common carotid artery was perfused with serum containing 14 C-4-cholesterol linked with lipoprotein; the fluid mechanics resembled those described above. In 20 experiments, there was no spatial dependence of uptake of the label, flux was lower by a factor of about a hundred than that predicted, and there was a suggestion (statistically nonsignificant) of shear dependence. The first two findings are inconsistent with transport controlled by the diffusion boundary layer. An uptake-controlled transport could be shear dependent.KEY WORDS boundary layer atheroma wall shear lipoprotein artery• Wall shear rate in arteries appears to vary spatially, and those regions which experience relatively high or relatively low wall shear can be identified. Moreover, the transport of certain materials between the intraluminal blood and the artery wall appears to be dependent on wall shear. The distribution of certain early atheromatous lesions in man, the accumulation pattern of lipid in arteries of animals on high-lipid diets, and the accumulation pattern of certain labeled materials in arteries correlate with wall shear ( 1 , 2). These observations relate to conditions in vivo where wall shear rate averaged over the cardiac cycle is essentially constant at any point, but the hypothesis of shear-dependent arterial transport gains support from evidence for enhanced flux of Evans blue dye to the wall following experimental elevation of wall shear in vivo ( 3 ) .

Profiles of velocity in coronary arteries of dogs indicate lower shear rate along inner arterial curvature.

“…Caro and associates 5 suggested that shear enhances mass transport by means of a steepening effect on the concentration gradient. Subsequently, however, Caro and Nerem 40 showed that cholesterol uptake by arteries is not limited by diffusion boundary layer conditions. In summary, velocity profiles in the left anterior descending and circumflex coronary arteries of dogs were skewed away from the inner wall.…”

Flow-dependent cellular mechanotransduction in atherosclerosis

“…Conversely, surgically converting a region of disturbed flow into one with high laminar flow can induce plaque regression even in the presence of high cholesterol (Stephanie Lehoux, McGill University, personal communication). It was initially hypothesized that low shear stress promotes atherosclerosis through increased mass transport at regions where residence times of solutes and cells was longer (Caro et al, 1971), but experimental studies revealed an opposite relationship (Caro and Nerem, 1973;Fry, 1969;Sill et al, 1995;Tarbell, 2003). How active sensing of physical forces by ECs leads to inflammatory activation of artery walls and progression to atherosclerosis is a subject of current research.…”

Quantification of coronary artery stenosis in vivo.

“…Recent studies by Friedman et al (1981), Zarins et al (1981Zarins et al ( , 1983, and Bharadvaj et al (1982) suggest that flow separation and instability favor atherogenesis, whereas increased flow velocity may be protective. However, Caro and Nerem (1973), Brown et al (1982), and Fry (1968Fry ( , 1969, hold the opposite point of view. The issue remains to be settled.…”