Flow-dependent accumulation of LDL in co-cultures of endothelial and smooth muscle cells in the presence of filtration flow through the cell layer.

To elucidate the roles of blood flow and transmural filtration flow in localized LDL accumulation in vascular walls, we studied the effects of flow velocity on LDL concentration at the cell surface and LDL uptake by co-cultures of vascular endothelial cells (ECs) and smooth muscle cells using a parallel-plate flow cell with or without filtration flow. Co-cultures were prepared on porous membranes. In the presence of filtration flow through the cell layer, the LDL concentration at the cell surface increased when the perfusion velocity was decreased (shear stress was decreased from 1.5 to 0.2 Pa). In the absence of filtration flow, LDL concentration remained unchanged despite changes in flow velocity. LDL uptake by the cells was proportional to its surface concentration that varied inversely with flow velocity. Therefore, in the presence of filtration flow, LDL accumulation was greater under conditions of low shear stress (0.2 Pa) than with high shear stress (1.5 Pa). In contrast, in the absence of filtration flow, LDL uptake was almost proportional to the magnitude of shear stress. These results suggest that shear stress- induced biological responses of ECs and transmural filtration flow, both play important roles in localized LDL accumulation in vascular walls.