The role of apoptosis in LDL transport through endothelial cell monolayers

We have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for more than 90% of the transport [1]. To explore the role of apoptosis in the leaky junction pathway, TNF alpha and cycloheximide (TNF alpha/CHX) were used to induce an elevated rate of apoptosis in cultured bovine aortic endothelial cell (BAEC) monolayers and the flux of LDL was measured. Treatment with TNF alpha/CHX induced a 14.8-fold increase in apoptosis and a 4.2-fold increase in LDL permeability. These increases in apoptosis and permeability were attenuated by treatment with the broad caspase inhibitor Z-VAD-FMK. Apoptosis increased by 4.8-fold and permeability increased by 2.2-fold when the monolayers were treated with TNF alpha/CHX and 100 mu M Z-VAD-FMK. These results demonstrate the potential of manipulating endothelial monolayer permeability by altering the rate of apoptosis pharmacologically.