Activation of Peripheral Blood CD14+ Monocytes Occurs in Diabetes

Abstract

Blood levels of inflammatory markers associated with endothelial dysfunction and atherosclerosis are increased in diabetic patients; the highest levels occur in poorly controlled diabetes. We investigated the activation state of peripheral blood monocytes in diabetes with respect to scavenger receptor (CD36) expression and monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and peroxisome proliferator-activated receptors mRNA expression. CD14؉ monocytes were isolated from peripheral blood of type 1 and type 2 diabetic patients with good (HbA 1c <7.0%) or poor (>9.4%) glycemic control and a group of nondiabetic subjects. Monocytes from diabetic subjects displayed increased CD36 cell surface expression (P < 0.0005) and increased uptake of oxidized LDL (P < 0.05). Monocyte chemoattractant protein-1 gene expression was increased in monocytes from both groups of diabetic subjects (P < 0.05). Both CD68 and peroxisome proliferator-activated receptor-␥ gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects). In poorly controlled diabetes, CD14؉ monocytes are functionally activated and show some of the differentiation markers associated with macrophages. These monocytes also demonstrate an increased ability for attachment to normal endothelial cells, one of the early stages in atherogenesis. Diabetes 54:2779 -2786, 2005 I t has become clear that inflammatory processes play a major role in atherogenesis and that the endothelium is intimately involved at all stages of atheroma formation. With this has come a major change in our understanding of the function of the endothelium as a diffuse organ, involved in prevention of thrombosis and in modulation of both relaxation and contraction of the blood vessels (1,2). Raised levels of the inflammatory marker C-reactive protein (CRP) are associated with altered endothelial function and arterial stiffness in healthy individuals (3,4) and are predictive of future coronary heart disease in healthy middle-aged men (5). Views on the importance of inflammatory markers have progressed to the extent that it has been suggested by some that CRP is a stronger predictor of first cardiovascular events than LDL cholesterol (6); however, others suggest a more cautious interpretation of available data (7). In vitro studies have shown that CRP induces endothelial cells to produce the inflammatory cytokine interleukin-6 (IL-6), which, at least in part, is responsible for upregulation of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) (8). CRP also induces production of monocyte chemoattractant protein-1 (MCP-1) by both endothelial (8) and vascular smooth muscle (9) cells; MCP-1 enhances the movement of mononuclear cells into the subendothelial space.Although a great deal has been published on vessel wall stiffness and the prevalence of inflammator...

Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells

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