Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis (p 789) Sortilin protein drives cholesterol uptake in macrophages and promotes

Sortilin protein drives cholesterol uptake in macrophages and promotes atherosclerosis, report Patel et al. A characteristic feature of atherosclerosis is the formation of foam cells that arise from cholesterol-loaded macrophages. But exactly how macrophages take up cholesterol from transporter proteins such as low-density lipoprotein (LDL) is unclear, especially since the deletion of known macrophage lipoprotein receptors in mice does not prevent foam cell formation. Patel and colleagues thus turned their attention to a protein called sortilin. This protein mediates hepatic LDL uptake and, through genome-wide association studies, has been linked with coronary artery disease. The function of sortilin in macrophages, however, was unknown. The team found that atherosclerosis-prone mice lacking sortilin—either in all cells or just macrophages—showed a significant reduction in the number of atherolsclerotic lesions compared to mice with normal levels of the protein. They also discovered that sortilinlacking macrophages exhibited a reduction in LDL uptake, while macrophages that over-expressed sortilin actually increased their LDL uptake. These results suggest that preventing the sortilin-driven uptake of LDL in macrophages might reduce foam cell formation and thus be a novel strategy for treating, and perhaps even preventing, atherosclerosis in the future. Transcriptional reversion of cardiomyocyte fate during mammalian cardiac regeneration (p 804)