Effect of low-density lipoprotein on endothelial cell membrane fluidity and mononuclear cell attachment.
To determine the effects of prolonged low-density lipoprotein (LDL) exposure in vitro on cultured endothelial cell (EC) lipid dynamics and cellular function, human umbilical vein ECs were incubated in LDL concentrations [cholesterol (Chol) = 240 mg/dl] associated with the premature development of atherosclerosis. After 4 days of incubation, cells were examined for changes in cellular lipid composition and for membrane fluidity. Results indicate that LDL-EC have increased Chol content (control EC vs. LDL-EC = 22.4 +/- 5.26 vs. 38.9 +/- 0.24 nmol/10(6) cells, P less than 0.05) and cellular Chol-to-phospholipid ratio (0.61 +/- 0.10 vs. 1.21 +/- 0.10 mol/mol, P less than 0.05). Augmentation of EC Chol content was accompanied by a marked decrease in EC cellular membrane fluidity as assessed by fluorescence polarization (anisotropy, r values, 0.172 +/- 0.019 vs. 0.226 +/- 0.014, P less than 0.0001). LDL-induced changes in EC lipid dynamics were associated with enhanced EC binding of monocytes (P less than 0.05) and U937 cells (P less than 0.01). Both LDL-induced decreases in membrane fluidity and enhanced attachment of mononuclear cells were reversed to control levels following a 2-min incubation of LDL-EC with the membrane mobility agent, A2C. These data therefore suggest that LDL-induced modulations in lipid dynamics play an important role in perturbation of EC function.
Pritchard
K A
KA
Department of Medicine, New York Medical College, Valhalla 10595.
Schwarz
S M
SM
Medow
M S
MS
Stemerman
M B
MB
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism; D014471:Umbilical Veins
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D002784:Cholesterol