High-density lipoprotein increases intracellular calcium levels by releasing calcium from internal stores in human endothelial cells Original Research Article

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 Cai) are investigated. We show that HDL, like low density lipoproteins (LDL), increases EC Cai 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 Cai. 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 Cai in response to HDL. These findings suggest that HDL, like LDL, can modulate EC Cai and that this occurs via a pertussis toxin-sensitive G protein-mediated pathway which involves phospholipase C.