Document Detail

The role of apoptosis in LDL transport through cultured endothelial cell monolayers.
MedLine Citation:
PMID:  19709659     Owner:  NLM     Status:  MEDLINE    
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.
Limary M Cancel; John M Tarbell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-08-07
Journal Detail:
Title:  Atherosclerosis     Volume:  208     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-15     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  335-41     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Amino Acid Chloromethyl Ketones / pharmacology
Aorta / cytology
Biological Transport
Cycloheximide / pharmacology
Endothelial Cells / cytology*
Lipoproteins, LDL / metabolism*
Models, Biological
Tight Junctions / metabolism
Tumor Necrosis Factor-alpha / metabolism
Water / chemistry
Grant Support
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Lipoproteins, LDL; 0/Tumor Necrosis Factor-alpha; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 059QF0KO0R/Water; 98600C0908/Cycloheximide

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