Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment.

BACKGROUND: The inflammatory/antiinflammatory properties of HDL were compared with HDL cholesterol in 2 groups of patients and in age- and sex-matched control subjects. METHODS AND RESULTS: Group 1 consisted of 26 patients not yet taking a statin who presented with coronary heart disease (CHD) or CHD equivalents by National Cholesterol Education Program Adult Treatment Panel III criteria studied before and 6 weeks after 40 mg/d of simvastatin. Group 2 consisted of 20 patients with documented CHD and HDL cholesterol > or =84 mg/dL. The inflammatory/antiinflammatory properties of HDL were determined by the ability of the subject's HDL to alter LDL-induced monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction of MCA by a control LDL was determined in the absence or presence of the subject's HDL. Values in the absence of HDL were normalized to 1.0. Values >1.0 after the addition of HDL indicated proinflammatory HDL; values <1.0 indicated antiinflammatory HDL. Group 1 values before simvastatin were LDL cholesterol, 118+/-24 mg/dL; HDL cholesterol, 57+/-13 mg/dL; triglycerides, 125+/-64 mg/dL; and high-sensitivity C-reactive protein (hs-CRP), 1.7+/-1.9 mg/L; and MCA values were 1.38+/-0.91, compared with 0.38+/-0.14 for control subjects (P=1.5x10(-5)). After simvastatin, values were LDL cholesterol, 73+/-24 mg/dL; HDL cholesterol, 61+/-14 mg/dL; triglycerides, 99+/-52 mg/dL; and hs-CRP, 1.3+/-1.3 mg/L; and MCA values were 1.08+/-0.71. In group 2, values were LDL cholesterol, 108+/-34 mg/dL; HDL cholesterol, 95+/-14 mg/dL; triglycerides, 89+/-44 mg/dL; and hs-CRP, 0.8+/-0.7 mg/L; and MCA values were 1.28+/-0.29, compared with 0.35+/-0.11 for control subjects (P=1.7x10(-14)). Similar results were obtained with the cell-free assay. CONCLUSIONS: The inflammatory/antiinflammatory properties of HDL distinguished patients from control subjects better than HDL cholesterol and were improved with simvastatin.

Identification of genes induced by oxidized phospholipids in human aortic endothelial cells.

Oxidized-L-alpha-1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-Phosphorylcholine (Ox-PAPC), a component of mildly oxidized/minimally modified low-density lipoprotein (MM-LDL), accounts for many of the biological activities of MM-LDL. Having hypothesized that Ox-PAPC initiates gene expression changes in endothelial cells that result in enhanced endothelial/monocyte interactions and the subsequent development of atherosclerotic lesions, we used the suppression subtractive hybridization (SSH) procedure to compare mRNA isolated from PAPC-treated human aortic endothelial cells (HAEC) with mRNA isolated from Ox-PAPC-treated cells. Genes induced by Ox-PAPC but not by PAPC in HAEC included genes involved in signal transduction, extracellular matrix, growth factors, chemokines and several genes with unknown functions. The observed pattern of gene induction suggests that Ox-PAPC may play multiple roles in angiogenesis, atherosclerosis, and inflammation and wound healing.