Concentration polarization of oxidative modification of low-density lipoproteins: Its effect on oxidative modification of low-density lipoprotein uptake and apoptosis of the endothelial cells

There is increasing evidence suggesting that oxidative modification of low-density lipoprotein (ox-LDL) in the vessel wall plays a crucial role in the initiation and progression of atherogenesis. The purpose of this study is to substantiate our hypothesis that concentration polarization of ox-LDL may also occur in the arterial system, which in turn can lead to enhanced endothelial cell (EC) apoptosis and induce atherogenesis. Using a parallel-plate flow chamber technique, ox-LDL uptake and apoptosis of the human ECs cultured on permeable or nonpermeable membranes were analyzed. The experimental results showed that 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indocarbocyanine (DiI)-ox-LDL uptake by the ECs increased with increasing concentration of DiI-ox-LDL in the perfusion solution. The overall average value of DiI-ox-LDL uptake was ∼20% higher for the permeable group than that for the nonpermeable group. The results also showed that ox-LDL induced ECs death and apoptosis in the permeable group were ∼12% and 26% higher than those in the nonpermeable group, respectively. The results from the in vitro model study, therefore, support our hypothesis that concentration polarization of ox-LDLs may occur in the arterial system. In conclusion, the occurrence of ox-LDL concentration polarization could enhance ox-LDL infiltration into the arterial wall and accelerate EC apoptosis.