Ca Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis.

In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca enhances the secretion of anti-inflammatory cytokines. Various Ca antagonists have been seminal for the demonstration of the role of Ca in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca and efferocytosis in atherosclerosis and to evaluate cellular Ca fluxes as potential treatment targets in atherosclerotic cardiovascular diseases.