ABSTRACT
BACKGROUND AND OBJECTIVES: Inflammation and activation of immune cells play important roles in the pathogenesis of atherosclerosis. We investigated the activation status of plasma inflammatory markers and immune cells in angina patients. METHODS: We analyzed the plasma level of C-reactive protein (CRP) as a marker of inflammation in 24 patients with angina pectoris (12 unstable angina, 12 stable angina), and 12 normal subjects. The degree of activation of peripheral blood monocytes was assessed by Northern analysis of pro-atherogenic cytokines and the activation status of T-lymphocytes was measured by flow-cytometric analysis of HLA-DR expression on T-cells. RESULTS: Plasma level of CRP was highest in 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 CRP level and the occurrence of minor and major coronary events during 6 months of follow-up. The percentage of HLA-DR positive T-lymphocyte was significantly increased in the unstable angina patients (26.8+/-1.4%) compared with that in the control (14.7+/-1.2%)(p=0.0053). When baseline levels of cytokine mRNA were measured in monocytes, the percentages of the patients expressing higher than normal levels of IL-8, IL-1b, MCP-1, and TF mRNAs was 37.5, 29.2, 33.3, and 37.5%, respectively (p=0.0143, 0.0371, 0.0233, and 0.0143, respectively). Basal mRNA levels of interleukin (IL)-8, tissue factor (TF), IL-1b and monocyte chemoattractant protein-1 (MCP-1) showed a strong correlation with each other (p<0.01 in all combination) but not with tumor necrosis factor (TNF)-alpha or transforming growth factor (TGF)-beta1. CONCLUSION: We observed increase in plasma CRP levels and activation of T-lymphocytes in angina patients. These results may help further classification of angina patients according to the activation of inflammatory markers and understanding the prognosis of the disease.
Subject(s)
Humans , Angina Pectoris , Angina, Unstable , Atherosclerosis , C-Reactive Protein , Chemokine CCL2 , Classification , Cytokines , Follow-Up Studies , HLA-DR Antigens , Inflammation , Interleukin-8 , Interleukins , Monocytes , Plasma , Prognosis , RNA, Messenger , T-Lymphocytes , Thromboplastin , Transforming Growth Factors , Tumor Necrosis Factor-alphaABSTRACT
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.