Concentration Polarization of Low Density Lipoproteins (LDL) in the Arterial System^a

Abstract

The atherogenic lipid concentration at the luminal surface of a blood vessel may vary according to its location in the arterial tree because of regional differences in wall shear rate, blood pressure, and vascular permeability. We therefore hypothesized that these local variations in the luminal surface lipid concentration may contribute to the localization of atherosclerosis. To verify this hypothesis, the transport of low-density lipoproteins from flowing blood to the arterial wall was studied numerically under both steady-state and pulsatile flow conditions. Numerical analysis predicted that "concentration polarization" of LDL may occur in the arterial system under these conditions. In contrast to steady-state flow conditions, the luminal surface LDL concentration varied with time in a cardiac cycle. However, its time-average value was slightly higher than the corresponding value under steady-state flow conditions. The time-average value of the luminal surface LDL concentration was 5 to 14% greater than the bulk concentration in a straight segment of an artery. The luminal surface LDL concentration at the arterial wall was flow-dependent, varying linearly with the filtration rate through the vessel wall and inversely with wall shear rate. This may therefore have some significant implications for the pathogenesis and localization of vascular disorders.

Two-photon microscopy of aorta fibers shows proteolysis induced by LDL hydroperoxides

“…In plaques, the arterial matrix network is almost fully destroyed, and plaque-free areas display alteration similar to that observed in our ex vivo model. An appealing suggestion from these data is that oxidatively modified LDL leads to diffuse damage of vascular matrix, similar to the vasculopathy of aging, but plaque formation occurs only in discrete focal areas, in agreement with the suggestion that other elements, e.g., shear stress, are likely to be involved in plaque formation [37]. The more severe degradation of the fibrillar network observed under the plaque (Fig.…”

Modelling and simulation of low-density lipoprotein transport through multi-layered wall of an anatomically realistic carotid artery bifurcation

“…It is important to note that simulation revealed the concentration polarization (or Staverman filtration mechanism) (an increase in the concentration levels compared with its inlet values) at the lumen-endothelium interface (figure 3a). This is caused by the higher mass transfer resistance imposed by the endothelium, as demonstrated in [25][26][27][28]. A radial profile of the LDL concentration (started at x/L ¼ 0.5 from the artery inlet) is shown in figure 3b.…”

Oxygen transfer in human carotid artery bifurcation

“…It has been well documented that atherosclerotic stenosis of carotid artery preferentially occurs in the region of carotid sinus, where blood flow is disturbed resulting in low wall shear zones and elevated wall concentration of atherogenic lipids [14,19]. In the present study, we studied oxygen transfer in the carotid bifurcation.…”

“…This may lead to enhanced lipid infiltration into the vascular wall and upregulate vascular endothelial growth factor (VEGF) in vascular smooth muscle cells [16][17][18]. The increased permeability of lipids at the low oxygen supply sites may also lead to local variations in the luminal surface lipid concentration which may contribute to the localization of atherosclerosis [19].…”