Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood

Abstract

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBC to high-density lipoprotein (HDL), while cholesterol from low-density lipoprotein (LDL) moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBC and plasma lipoproteins was saturable, temperature-, energy- and time-dependent consistent with an active process. We did not find LDL receptor, ATP-binding cassette transporter G1 or scavenger receptor class B type 1 in RBC but found a substantial amount of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apolipoprotein A-I (apoA-I) was negligible and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL or plasma. Cholesterol efflux from and cholesterol uptake by RBC from Abca1+/+ and Abca1-/- mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBC and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, Lipoprotein Lipase and Mitochondrial Translocator Protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBC remains uncertain.

Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation

“…Cholesterol plays a crucial role in the cell membrane structure and function. Recently, the intensive exchange of cholesterol molecules on the surface of red blood cells was described in detail [ 33 ]. Although the proportion of circulating monocytes is smaller compared to red blood cells, the inflow and outflow of LDL cholesterol was proven [ 33 ].…”

“…Recently, the intensive exchange of cholesterol molecules on the surface of red blood cells was described in detail [ 33 ]. Although the proportion of circulating monocytes is smaller compared to red blood cells, the inflow and outflow of LDL cholesterol was proven [ 33 ]. Increased cholesterol commutation in circulating monocytes drives them to macrophage maturation [ 33 ].…”

“…Although the proportion of circulating monocytes is smaller compared to red blood cells, the inflow and outflow of LDL cholesterol was proven [ 33 ]. Increased cholesterol commutation in circulating monocytes drives them to macrophage maturation [ 33 ]. Similar changes in macrophage cells residing in adipose tissue might be expected.…”

“…This effect is direct, as we found a direct effect of statins on the macrophage polarization in vitro. The direct effects of intra-vasal concentrations of cholesterol and its raft cell membrane content were recently documented in red blood cells [ 33 ]. We can expect a similar scenario in circulating monocytes, as well as in residential macrophages in adipose tissue.…”

The major pathways of lipids (triglyceride and cholesterol) and lipoprotein metabolism

“…Lipoproteins serve as an address tag that play a significant role in transportation of cholesterol from and to tissues, thus LDL carries blood cholesterol from liver to other tissues known as bad cholesterol, inversely, HDL carries blood cholesterol from other tissues to the liver known as good cholesterol (Figure 2) (Ohkawa et al, 2020).…”