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 preve nt the development of atherosclerosis. The intracellular signaling mechanis ms activated by HDL in vascular cells are currently under active investigat ion. In this study the effects of HDL on endothelial intracellular Ca level s (EC Ca,) are investigated. We show that HDL, like low density lipoprotein s (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 Ca,. HDL appeared to r elease Ca from the same internal stores as did LDL, since preincubation of EC with LDL prevented subsequent responses to HDL but not to the vasodilato r 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, in response to HDL. These findings suggest that HDL, like LDL, can modulate EC Ca, and that this occurs via a pertussis to xin-sensitive G protein-mediated pathway which involves phospholipase C. (C ) 1999 Elsevier Science Ireland Ltd. All rights reserved.