The effect of estrogen on low-density lipoprotein binding kinetics in aortic endothelial cells.
The inhibition of atherosclerosis by estrogen has been shown clinically and experimentally, but the mechanism by which this occurs is unknown. Previous studies have shown that estrogen enhances the uptake of low-density lipoprotein (LDL) by bovine aortic endothelial cells (BAEC) while not altering membrane binding at saturating levels of LDL. In this study the effect of estrogen on LDL binding kinetics has been investigated. Computer-assisted Scatchard analysis of binding data suggests a single-site binding model. Estrogen-treated BAEC showed a lower binding affinity (Ka = 2.47 +/- 0.74 E7 M-1) than control cells (1.95 +/- 0.21 E7 M-1) (p = 0.0012). Estrogen-treated cells, however, had a greater binding capacity (Bmax = 1.26 +/- 0.07 E-10M) than control cells (Bmax = 8.49 +/- 0.44 E-11M) (p = 0.0004). The latter was due primarily to a difference in LDL binding at higher concentrations of LDL (greater than 40 micrograms/ml). These findings are consistent with an estrogen-stimulated increase in low-affinity binding of LDL to BAEC, which may not be directly receptor mediated and which appears to enhance the uptake of LDL at higher lipoprotein concentrations. Such alterations in LDL uptake by endothelial cells could influence the formation of atherosclerotic plaque.
Alexander
J J
JJ
Case Western Reserve University School of Medicine, Cleveland, Ohio.
Hoenig
M
M
Graham
D
D
Imbembo
A L
AL
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001665:Binding Sites; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D004958:Estradiol