Relationship between the HDL composition and its anti-inflammation function in patients with diabetes and coronary heart disease

Abstract

Objective In this case-control study we enrolled healthy subjects and subjects with type 2 diabetes mellitus (DM), coronary heart disease(CHD) only, or both disorders. The objective is to study the inhibition of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1) expression and the cell adhesion by high density lipoprotein(HDL) in different groups; and to investigate the relationship between the level of HDL-serum amyloid A (SAA) and anti-adhesion function. Methods HDLs were isolated from plasma with ultracentrifugation.The levels of lipoprotein-associated SAA and apolipoprotein A-Ⅰ (apoAⅠ) were detected with Enzyme-Linked Immuno Sorbent Assay(ELISA). Human umbilical vein endothelial cells (HUVECs) were incubated with HDLs and stimulated with TNF-α, then labeled with antiCD54-PE, or antiCD106-FITC monoclonal antibodies respectively, then incubated with THP-1 cells, which were labeled by calcein-AM antibody.The expression of cell-surface molecules and the number of adhering THP-1 cells were measured as fluorescence intensity by flow cytometer. Results The levels of HDL-SAA in the healthy controls were lower than patients with DM only and CHD only [(4.89±1.46) ng/μg vs. (22.54±7.40) ng/μg and (13.28±5.05) ng/μg, both P<0.05]. The HDLs of all groups could inhibit the expression of ICAM-1, VCAM-1, while the HDLs obtained from healthy subjects could inhibit the expression of ICAM-1 significantly greater than HDLs obtained from DM and DM+ CHD subjects (17 318.60±4 364.77 vs. 34 171.67±13 918.07 and 39 633.60±8 728.22, both P<0.05), and the inhibition of VCAM-1 expression by normal HDLs was significantly greater than HDLs obtained from DM+ CHD subjects (244.80±119.55 vs.388.80±75.76, P=0.04). The HDLs of all groups could inhibit the adhesion of THP-1. The HDLs from healthy subjects could inhibit the adhesion of THP-1 significantly greater than those from DM, CHD and DM+ CHD subjects (503.24±63.50 vs. 2 918.00±0.00, 1 510.33±1 353.87 and 4 196.50±412.60, all P<0.05). The level of HDL-SAA was correlated to the level of ICAM-1 expression (the regression coefficient was 1.57, t=3.22, P<0.01) and THP-1 adhesion (the regression coefficient was 1.16, t=3.05, P=0.01). In addition, the level of apoAⅠwas reversely correlated with the level of ICAM-1 expression (the regression coefficient was -0.35, t=-2.40, P=0.02). Conclusions The levels of ICAM-1, VCAM-1 expression and THP-1 adhesion induced by HDL are significantly attenuated in DM subjects and CHD subjects, which are positively correlated with the level of HDL-SAA and reversely correlated with the level of apoAⅠ. Key words: Atherosclerosis; Diabetes mellitus; Lipoproteins, HDL; Cell adhesion molecules; Serum amyloid A protein; Apolipoprotein A-Ⅰ