Atherosclerosis is an inflammatory disease. Platelet-endothelium interaction plays an important role in the pathophysiology of atherogenesis. We investigated the role of activated platelets for secretion of interleukin (IL)-1beta, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha and expression of intercellular adhesion molecule (ICAM)-1 on endothelial cells. Human umbilical vein endothelial cells (HUVEC) were incubated with non-stimulated or ADP-activated platelets for 6 hr. Secretion of interleukin (IL)-1beta, MCP-1 and MIP-1alpha and surface expression of ICAM-1 were measured by ELISA and flow cytometry. In the presence of activated platelets, the secretion of IL-1beta, MCP-1, and MIP-1alpha and surface expression of ICAM-1 were significantly increased compared with non-activated platelets. The present study shows that activated platelets may contribute to expression of various inflammatory mediators on endothelial cells.
Blood Platelets/metabolism* ; Cells, Cultured ; Cells, Cultured ; Endothelium, Vascular/secretion* ; Endothelium, Vascular/cytology ; Human ; Intercellular Adhesion Molecule-1/biosynthesis ; Interleukin-1/secretion* ; Macrophage Inflammatory Protein-1/secretion* ; Monocyte Chemoattractant Protein-1/secretion* ; Platelet Activation/physiology*

Atherosclerosis is an inflammatory disease. Platelet-endothelium interaction plays an important role in the pathophysiology of atherogenesis. We investigated the role of activated platelets for secretion of interleukin (IL)-1beta, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha and expression of intercellular adhesion molecule (ICAM)-1 on endothelial cells. Human umbilical vein endothelial cells (HUVEC) were incubated with non-stimulated or ADP-activated platelets for 6 hr. Secretion of interleukin (IL)-1beta, MCP-1 and MIP-1alpha and surface expression of ICAM-1 were measured by ELISA and flow cytometry. In the presence of activated platelets, the secretion of IL-1beta, MCP-1, and MIP-1alpha and surface expression of ICAM-1 were significantly increased compared with non-activated platelets. The present study shows that activated platelets may contribute to expression of various inflammatory mediators on endothelial cells.
Blood Platelets/metabolism* ; Cells, Cultured ; Cells, Cultured ; Endothelium, Vascular/secretion* ; Endothelium, Vascular/cytology ; Human ; Intercellular Adhesion Molecule-1/biosynthesis ; Interleukin-1/secretion* ; Macrophage Inflammatory Protein-1/secretion* ; Monocyte Chemoattractant Protein-1/secretion* ; Platelet Activation/physiology*

Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the plasma levels of inflammatory markers and the degree of activation of peripheral blood monocytes and T-lymphocytes isolated from 12 unstable angina, 12 stable angina, and 12 normal subjects. In 20%-33% of patients, monocytes expressed high basal levels of IL-8, tissue factor, IL-1beta, and monocyte chemoattractant protein-1 mRNA. Furthermore, basal mRNA levels of these cytokines showed strong correlation with each other (p < 0.01 in all combination) but not with tumor necrosis factor-alpha or transforming growth factor-beta1. Plasma level of C-reactive protein was highest in the unstable angina patients (1.63+/-0.70 mg/l) and lowest in the control subjects (0.22+/-0.08 mg/l) (P = 0.03). We also observed a high correlation between C-reactive protein level and the occurrence of minor and major coronary events during 6 months of follow-up. Activation status of T-cells, assessed by the percentage of HLA-DR positive cells, was highest in the unstable angina patients (26.8+/-1.4%) compared with that in the control (14.7+/-1.2%) (P = 0.0053). Our data represent the first case showing that the circulating monocytes in angina patients are activated to a state express numerous proatherogenic cytokines. These results may help to diagnose angina patients according to the inflammatory markers and evaluate the prognosis of the disease.
Aged ; Angina Pectoris/immunology* ; Angina Pectoris/diagnosis ; Angina, Unstable/immunology* ; Angina, Unstable/diagnosis ; Biological Markers/blood ; C-Reactive Protein/analysis ; Cytokines/blood* ; Female ; HLA-DR Antigens/immunology ; Human ; Interleukins/blood ; Lymphocyte Transformation ; Male ; Middle Age ; Monocyte Chemoattractant Protein-1/blood ; Monocytes/metabolism* ; RNA, Messenger/metabolism ; T-Lymphocytes/metabolism* ; Transforming Growth Factor beta/analysis ; Tumor Necrosis Factor/analysis