The development and pro
gression of atherosclerosis and its predisposition for unstable an
gina, myocardial infarction and stroke is associated with traditional risk factors such as family history, ci
garette smokin
g, hypertension, dyslipidemia, diabetes mellitus, obesity, imbalance of the hemostatic/fibrinolytic system and sedentary lifestyle. However, much of the variability in atherosclerosis and its manifestations still remains unexplained. Nowadays, there is increasin
g evidence that immunolo
gic mechanisms play a major role in etiolo
gy, prediction of coronary plaque instability and foreseein
g severe reaction leadin
g to an actual coronary event. Cells of the immune system such as macropha
ges, mast cells and T-lymphocytes are major components of human atheromatous plaque. These cells participate in a vicious immune cycle and activate each others via bidirectional stimuli. For example, mast cells can activate macropha
ges and may enhance T-cell activation. Inducible macropha
ge protein 1a may activate mast cells, while CD169+ macropha
ges activate CD8 T cells. T cells may mediate mast-cell activation and proliferation and re
gulate macropha
ge activity.
Mediators secreted by these cells, including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines, can induce coronary artery spasm and atheromatous plaque erosion and rupture, culminating in the development of acute coronary syndromes.