LAUSR

April 16, 2019 1979 Nicola Potere, MD Stefano Toldo, PhD Antonio Abbate, MD, PhD To the Editor: We have read with interest the report by Mueller and colleagues1 suggesting that LRP1 (low-density lipoprotein receptor-related protein 1) in macrophages promotes atherosclerosis. They show that mice with an inducible deletion of LRP1 in macrophages have a reduced transition from the M1 to M2 phenotype, and this is associated with larger atherosclerotic burden. We welcome this contribution to the field because it adds to the complexity of the role of LRP1 in atherosclerosis, and in health and disease in general. We would, however, want to make sure that the readers have a comprehensive view of the role of LRP1 as a complex multifunctional receptor with important scavenger and anti-inflammatory functions.2 Recent data on the role of LRP1 in macrophages show that LRP1 possesses both antiand proinflammatory properties in a ligand-specific manner.3 LRP1 agonists also have been shown to have prosurvival and anti-inflammatory effects in models of acute injury.4,5 Therefore, we would think that the excellent report by Mueller et al1 warrants a disclaimer that the absence of macrophage LRP1 unexpectedly accelerates atherosclerosis regression and enhances reverse cholesterol transport in a specific mouse model of apolipoprotein E–deficient mice on a high-fat diet for 12 weeks. It is worth noting that LRP1 is also known as apolipoprotein E receptor, and, thus, one question that would come to mind is whether the same effect would be seen in a different model of atherosclerosis and, in general, in a different model of injury.