Correlation between the decrease of cholesterol efflux from macrophages in patients with type II diabetes mellitus and down-regulated CYP7A1 expression

• Published in: Genetics and molecular research 2015-07, Vol.14 (3), p.8716-8724
• Main Authors: Bao, L D, Li, C Q, Peng, R, Ren, X H, Ma, R L, Wang, Y, Lv, H J
• Format: Article
• Language: English
• Subjects: Adult; ATP Binding Cassette Transporter, Sub-Family G, Member 5; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Case-Control Studies; Cells, Cultured; Cholesterol - blood; Cholesterol - secretion; Cholesterol 7-alpha-Hydroxylase - genetics; Cholesterol 7-alpha-Hydroxylase - metabolism; Coronary Disease - blood; Coronary Disease - enzymology; Coronary Disease - etiology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - enzymology; Down-Regulation; Enzyme Repression; Female; Humans; Lipoproteins - genetics; Lipoproteins - metabolism; Liver X Receptors; Macrophages - enzymology; Macrophages - secretion; Male; Middle Aged; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/2015.July.31.20

The purpose of this study was to examine the changes of cellular cholesterol efflux from macrophages in patients with type II diabetes mellitus (DM), and to determine the expression of CYP7A1, ABCG5, and LXRβ therein. We recruited 30 patients with type II DM (including 15 patients complicated with coronary heart disease and 15 patients with DM only) and 15 normal controls for this study. Peripheral blood monocytes were isolated for macrophage culture. The mRNA and protein expression levels of CYP7A1, ABCG5, and LXRβ were determined using real-time polymerase chain reaction and western blot. The macrophage cholesterol efflux rate was determined with 10% autoserum and standard serum as receptors. We determined that the expression levels of macrophage CYP7A1 mRNA and protein in the type II DM group were significantly lower than those in the control group, but no differences were found in the ABCG5 and LXRβ expression levels between the groups. The macrophage cholesterol efflux rate in the patients with type II DM was also significantly decreased compared with that of the normal control subjects (P < 0.01). Furthermore, CYP7A1 mRNA expression and macrophage cholesterol efflux rate were significantly positively correlated. In summary, this study demonstrated that the macrophage cholesterol efflux in patients with type II DM was significantly reduced, and that this reduction was associated with the down-regulation of CYP7A1 expression.