The presence of small dense low-density lipoprotein subfractions in human serum induce the accumulation of cholesterol by monocyte-like THP-1 cells

Abstract

The aim of the study was to investigate the accumulation of total cholesterol (TC) in human macrophages depending on the subfractions’profile of apoBIOO-containing lipoproteins. Materials and methods. THP-1 cells were incubated for 24 hours with human serum samples with TC level 240 mg/dl after macrophage differentiation. The supernatant was removed, the cells washed and lysed. The concentration of TC and totalprotein were measured by the colorimetricmethod in cell lysates. Thefollowing data were determined in the sera: the concentration of lipcproteinfractions and subfractions by method of native polyacrylamide gel electrophoresis, B-100 apoprotein, circulating immune complexes (CIC), the content of oxidised low density lipoproteins (oxLDL) and titerof autoantibodies (autoAb) to oxLDL. Results. Sera samples were divided into three groups depending on the concentration of subfractions of small dense hw-density lipoproteins (sdLDL): group 1 - without sdLDL (n = 11'); group 2 - with the concentration of sdLDL from 1 to 4.9 mg/dl (n - 13); group 3 - with the concentration of sdLDL> 5 mgjdl (n=11) - atherogenic profile B. In the sera of group 3 relative to group 1, higher levels of apoB-100 (median, [25%, 75%] - 68.1 mg/dl [63.8, 84.1] and 58.6 mg/dl [43.9, 62.4], p<0.01) and giant CICs (26.2 lab units [14.3, 31.8] and 11.3 lab units [9.7, 12.8],p - 0.03), were found respectively. When cells were incubated in the presence of sera with an atherogenic profile B, the level of TC in the lysate normalised to the protein, was significantly higher than in the group without sdLDL (6.5 rel. units [3.9, 9.1] and 2.7 rel. units [2,1, 3.9], p = 0,03). The data of multivariate analysis with includinginto the model the values of TC, high-density lipoprotein cholesterol, apoB-100, oxLDL and medium size LDLparticles (LDL-2) showed thatonly the concentration of sdLDL (r- 0.709,p< 0.001) worked as the independentpredictorof accumulation of TC. “ When incubating the cells with the sera from patients with sdLDL concentration more than 1 mg/dl, the increased - amountof TCin lysates wasfound even in thepresence of the so-called non-atherogenicprofileA. Conclusion. Thepresence of sdLDL even in small (less than 5 mg/dl) concentrations and independently of other components of the blood serum causes the accumulation of cholesterol by THP-1 cells.