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.

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment.

Five triphenyltriphenylamines with various substituents were investigated as precursors for near-infrared absorbing materials. Cyclic voltammetry (CV) studies showed that they all give stable radical cations in solution. The radical cations obtained by one-electron chemical oxidation of these compounds show strong absorption in the near-infrared region, and the position of the absorption is strongly influenced by the substituent. DFT (density functional theory) calculations suggest that the introduction of stronger electron-donating substituents would result in a smaller HOMO–SOMO energy gap and thus a larger long wavelength shift, which is consistent with the experimental results. On the other hand, strong electron-withdrawing substituents increase the HOMO–SOMO energy gap, resulting in a short wavelength shift. The position of the near-infrared absorption peak of the triphenylamine radical cation can be controlled to the longer or shorter wavelength direction depending on the substituent. A molecular design of near-infrared absorbing dyes utilizing the electronic effects of substituents is described.

Aims The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-atherogenic effects, we used 123I-labeled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT. Methods and results We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4 °C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labeled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labeled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analyzed the expression of known oxLDL receptors (e.g., SR-A, CD36, LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT. Conclusion We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.