Generation of intracellular signals by low density lipoprotein is independent of the classical LDL receptor.
Low density lipoprotein cholesterol (LDL) and apolipoprotein B-100 (1 to 15 micrograms/mL) had no significant influence on the inositol-1,4,5-trisphosphate (InsP3) formation in vascular smooth muscle cells and fibroblasts. Low density lipoprotein cholesterol (15 micrograms/mL) induced an elevation of intracellular Ca2+ from 85 to approximately 210 nmol/L in vascular smooth muscle cells from rat aorta in the absence or in the presence of 15 micrograms/mL monoclonal antibodies against the classical low density lipoprotein receptor or in the presence of apolipoprotein B-100. Moreover, in both human cultured fibroblasts from normocholesterolemic individuals and from patients with familial hypercholesterolemia homozygote class 1, LDL induced a dose-dependent rise of free intracellular calcium and a biphasic change of intracellular pH. Since homozygote class 1 fibroblasts are classical LDL receptor negative, and as antibodies against this receptor, as well as apolipoprotein B-100, did not attenuate the LDL-induced elevation of cytosolic calcium, we conclude that LDL might modify vascular activity via the observed intracellular changes without involving the classical low density lipoprotein receptor.
Sachinidis
A
A
Medical Policlinic, Universtät Bonn, Germany.
Locher
R
R
Vetter
W
W
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology*; D002478:Cells, Cultured; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D011973:Receptors, LDL / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D007295:Inositol Phosphates; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002118:Calcium