High-density lipoprotein increases intracellular calcium levels by releasing calcium from internal stores in human endothelial cells.
Elevated levels of high-density lipoproteins (HDL) appear to delay or prevent the development of atherosclerosis. The intracellular signaling mechanisms activated by HDL in vascular cells are currently under active investigation. In this study the effects of HDL on endothelial intracellular Ca levels (EC Ca(i)) are investigated. We show that HDL, like low density lipoproteins (LDL), increases EC Ca(i) in a dose-dependent fashion by releasing Ca from internal stores. Neither apolipoprotein A-I (apo A-I) nor apolipoprotein A-II (apo A-II) was responsible for the increase in EC Ca(i). HDL appeared to release Ca from the same internal stores as did LDL, since preincubation of EC with LDL prevented subsequent responses to HDL but not to the vasodilator ATP. In addition, preincubation of EC with pertussis toxin, an inhibitor of specific G proteins, as well as U73122, an inhibitor of phospholipase C, prevented a rise in EC Ca(i) in response to HDL. These findings suggest that HDL, like LDL, can modulate EC Ca(i) and that this occurs via a pertussis toxin-sensitive G protein-mediated pathway which involves phospholipase C.
Honda
H M
HM
Department of Medicine, University of California, Los Angeles 90095-1679, USA. hhonda@mednet.ucla.edu
Wakamatsu
B K
BK
Goldhaber
J I
JI
Berliner
J A
JA
Navab
M
M
Weiss
J N
JN
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001054:Apolipoproteins A / Q000378:metabolism / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D002478:Cells, Cultured / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D037342:Pertussis Toxin; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008075:Lipoproteins, HDL; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium