The role of apoptosis in LDL transport through cultured endothelial cell monolayers.
نویسندگان
چکیده
We have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for low density lipoprotein (LDL) transport under convective conditions, accounting for more than 90% of the transport [Cancel LM, Fitting A, Tarbell JM. In vitro study of LDL transport under pressurized (convective) conditions. Am J Physiol Heart Circ Physiol 2007;293:H126-32]. To explore the role of apoptosis in the leaky junction pathway, TNFalpha and cycloheximide (TNFalpha/CHX) were used to induce an elevated rate of apoptosis in cultured bovine aortic endothelial cell (BAEC) monolayers and the convective fluxes of LDL and water were measured. Treatment with TNFalpha/CHX induced a 18.3-fold increase in apoptosis and a 4.4-fold increase in LDL permeability. Increases in apoptosis and permeability were attenuated by treatment with the caspase inhibitor Z-VAD-FMK. Water flux increased by 2.7-fold after treatment with TNFalpha/CHX, and this increase was not attenuated by treatment with Z-VAD-FMK. Immunostaining of the tight junction protein ZO-1 showed that TNFalpha/CHX treatment disrupts the tight junction in addition to inducing apoptosis. This disruption is present even when Z-VAD-FMK is used to inhibit apoptosis, and likely accounts for the increase in water flux. We found a strong correlation between the rate of apoptosis and the permeability of BAEC monolayers to LDL. These results demonstrate the potential of manipulating endothelial monolayer permeability by altering the rate of apoptosis pharmacollogicaly. This has implications for the treatment of atherosclerosis.
منابع مشابه
The role of mitosis in LDL transport through cultured endothelial cell monolayers
Cancel LM, Tarbell JM. The role of mitosis in LDL transport through cultured endothelial cell monolayers. Am J Physiol Heart Circ Physiol 300: H769–H776, 2011. First published December 17, 2010; doi:10.1152/ajpheart.00445.2010.—We (7) have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, account...
متن کاملLipoprotein Lipase Increases Low Density Lipoprotein Retention
Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of ...
متن کاملPassage of low density lipoproteins through monolayers of human arterial endothelial cells. Effects of vasoactive substances in an in vitro model.
The endothelium controls the influx of lipoproteins into the arterial wall, a process that may be disturbed in arteriosclerotic blood vessels. We have used an in vitro model to investigate the characteristics of the passage of low density lipoproteins (LDL) through monolayers of human arterial endothelial cells. Umbilical artery, aorta, or carotid artery endothelial cells were cultured on polyc...
متن کاملLDL-Cholesterol Increases the Transcytosis of Molecules through Endothelial Monolayers
Cholesterol has been identified as a causative factor in numerous pathologies including atherosclerosis and cancer. One of the frequent effects of elevated cholesterol levels in humans is the compromise of endothelial function due to activation of pro-inflammatory signalling pathways. While the mechanisms involved in endothelial activation by cholesterol during an inflammatory response are well...
متن کاملRabbit beta-migrating very low density lipoprotein increases endothelial macromolecular transport without altering electrical resistance.
Rabbit aortic endothelial cells (RAEC) were grown on micropore filters in a new device. This system allowed in situ measurement of transendothelial electrical resistance (TEER). The monolayers demonstrated a TEER of 14 +/- 1 omega X cm2 at confluence. No difference was seen in the transport of low density lipoproteins (LDL) across endothelial cell monolayers obtained from normal or Watanabe her...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Atherosclerosis
دوره 208 2 شماره
صفحات -
تاریخ انتشار 2010