Intracellular-free calcium dynamics and F-actin alteration in the formation of macrophage foam cells

The formation of macrophage foam cells, which is the key event in atherosclerosis, occurs by the uptake of oxidized low-density lipoprotein (Ox-LDL) via the scavenger receptor (CD36) pathway. Ca2+ plays an important role in atherosclerosis. However, in the spatiotemporal view, the correlation between kinetic changes of intracellular-free calcium ([Ca2+]i) and the cellular dysfunctions in the formation of macrophage foam cells has not yet been studied in detail. By the use of confocal laser scanning microscope and flow cytometer, we have detected Ca2+ dynamics, the assembly of F-actin, and the expression of CD36 under the exposure of U937-derived macrophages to Ox-LDL. The uptake of Ox-LDL significantly increased [Ca2+]i in U937-derived macrophages in both acute and chronic treatments (P < 0.01). In particular, the increases of the induced [Ca2+]i were different in the presence or absence of extracellular Ca2+ under acute exposure. A time-dependent rise in F-actin assembly and CD36 expression at 12 and 24 h was induced, respectively, by Ox-LDL. The spatiotemporal increases of [Ca2+]i induced by Ox-LDL probably have the key effect on the early phrase in the formation of macrophage foam cells.