The role of mitosis in LDL transport through cultured endothelial cell monolayers

We (7) have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for >90% of the transport. We (8) have also recently shown that the permeability of bovine aortic endothelial cell monolayers is highly correlated with their rate of apoptosis and that inhibiting apoptosis lowers the permeability of the monolayers to LDL. To explore the role of mitosis in the leaky junction pathway, the microtubule-stabilizing agent paclitaxel was used to alter the rate of mitosis, and LDL flux and water flux (J(v)) were measured. Control monolayers had an average mitosis rate of 0.029%. Treatment with paclitaxel (2.5 μM) for 1.5, 3, 4.5, or 6 h yielded increasing rates of mitosis ranging from 0.099% to 1.03%. The convective permeability of LDL (P(e)) increased up to fivefold, whereas J(v) increased up to threefold, over this range of mitosis rates. We found strong correlations between the mitosis rate and both P(e) and J(v). However, compared with our previous apoptosis study (8), we found that mitosis was only half as effective as apoptosis in increasing P(e). The results led us to conclude that while mitosis-related leaky junctions might play a role in the initial infiltration of LDL into the artery wall, the progression of atherosclerosis might be more closely correlated with apoptosis-related leaky junctions.