Letter to the Editor

Abstract

A crucial event in atherosclerosis is the formation of foam cells. Vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), macrophage chemoattractant protein-1 (MCP-1), and macrophage colony stimulating factor (M-CSF) are important molecules that contribute to foam cell formation. 1 Removal of excess free cholesterol from macrophages, neutralization of monocyte migration inhibitory factor (MIF), and reduction of proinflammatory cytokine concentrations are important goals for the prevention of foam cell formation and the development of atherosclerosis. 2,3 Increases in intracellular cAMP concentration inhibit the expression of ICAM-1 and VCAM-1, 4 decrease the production of MCP-1 5 and M-CSF, 6 increase the expression of antiinflammatory cytokines, and decrease the expression of MIF and proinflammatory interleukins. 7 In addition, cAMP analogs induce the ABCA1 secretory pathway, by which apolipoproteins (apoA-I) actively remove free cholesterol from cells; treatment of macrophages with cAMP analogs causes parallel increases in apo-I-mediated cholesterol efflux. 8 On the basis of the role of cAMP in the expression of proatherogenic and antiatherogenic molecules, we postulated that the intracellular cAMP concentrations of peripheral monocytes may be low in patients with coronary artery disease.We studied 80 patients with chronic stable angina (SA) who were consecutively admitted to our hospital, and 67 healthy age-matched healthy volunteers with no known coronary artery disease or risk factors. Coronary angiography was carried out with all patients Total plasma cholesterol (mg/dL), LDL-cholesterol (mg/ dL), and HDL-cholesterol (mg/dL) were measured by colorimetric methods (Sigma Diagnostics Inc). Serum interleukin (IL)-6 (pg/mL) was measured by enzyme immunoassay (EIA; Diagnostic Products Corporation).Peripheral blood mononuclear cells were separated from whole blood by density-gradient centrifugation on FicollPaque columns, and monocytes were isolated by magnetic separation technology (MACS, Miltenyi Biotec GmbH). Monocytes were resuspended in RPMI-1640 (Gibco) containing 10% fetal bovine serum and 10% pooled normal human serum, and were then counted in a Neubauer chamber and stored at Ϫ80°C. The monocyte pellet was lysed ultrasonically for 180 seconds, and the intracellular levels of cAMP (pmol/10 6 cells) were measured by ELISA (Cayman Chemical R&D Systems Europe; the intra-and interassay coeficient of variations have been determined at multiple points of the curve. The coefficient variation is less than 5% in the 0.2 to 10 pmol/mL range). The kit instructions were followed.Itracellular cAMP values (meanϮSD) were analyzed by the 2-tailed test for unpaired observations. The null hypothesis was rejected when PՅ0.05.The clinical characteristics of the patients at the time of admission are presented in the Table. Intracellular cAMP concentrations were significantly higher (Pϭ0.001) in controls compared with SA patients (controls, 0.28Ϯ0.15 pmol/ 10 6 cells; and SA patients, 0.13Ϯ...