Abstract
High-density lipoprotein (HDL) plays a main role in reverse cholesterol transport (RCT), one of the most important functions for preventing atherosclerosis. Recent reports have shown that red blood cells (RBCs) can be associated with RCT, an interaction facilitated by albumin. However, the RCT function of RBCs has not been thoroughly elucidated. In this study, the RCT function of RBCs was assessed using cholesterol efflux capacity (CEC) assays, in which [3H]-labeled cholesterol-loaded human acute monocytic leukemia (THP-1) macrophages were incubated with RBCs as a cholesterol acceptor in the presence or absence of HDL or its main component protein apolipoprotein A-I (apoA-I). The CEC of RBCs was found to be dose dependent, enabling uptake of cholesterol from THP-1 macrophages through apoA-I and HDL, and directly from apoA-I and HDL in medium without the presence THP-1 macrophages. Moreover, RBCs could exchange cholesterol with HDL in a bidirectional manner but could only exchange cholesterol with apoA-I in a single direction. Although albumin promoted the movement of cholesterol, synergistic effects were not observed for both apoA-I and HDL, in contrast to previous findings. These results strongly suggested that RBCs may play important roles in RCT by mediating cholesterol efflux as temporary cholesterol storage.
Acknowledgments
We thank Associate Professor Masayuki Hara (General Isotope Research Division, Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University) for generous assistance with our study. We also thank Otsuka Toshimi Scholarship Foundation for supporting S.-J. Lai during this study. This work was supported by a Grant-in-Aid for Young Scientists (B) and Fostering Joint International Research (B) from the Japan Society for the Promotion of Science (Funder Id: 10.13039/501100001691; grant nos 15K19174 and 16KK0198 to R. Ohkawa), and the Takeda Science Foundation for the Promotion of Scientific Research to R. Ohkawa.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2019-0244).
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