[Atherosclerosis, Chronic Inflammation, and Thrombosis: In Search of the Missing Link in Laboratory Medicine]

Atherosclerosis is one of the leading causes of death in Japan. With accumulating data from animal experiments, it has become recognized that atherosclerosis involves a chronic inflammatory process of the arterial wall with a dyslipidemic background. However, clinical applications utilizing this knowledge remain scarce. In spite of optimal interventional and pharmacologic therapies, the risk of recurrent ischemia remains high and novel therapies to prevent atherogenesis or detect atherosclerosis in the early stage are needed. One of the potential molecular inflammatory targets that may be clinically relevant is natural killer T cells (NKT cells). Sphingosine-1-phosphate(S1P), one of the biologically active sphingolipids, increases TNF-α production in NKT cells and induces the migration of NKT cells, suggesting that S1P can regulate inflammatory processes in atherogenesis. Patients with high plasma S1P levels exhibit high levels of plasma TNF-α, plasma antigen levels of plasminogen activator inhibitor (PAI) -1, the major physiologic inhibitors of fibrinolysis, and a reduced endothelial function as assessed by the flow-mediated dilation of brachial arteries (FMD). Also, recent advances in research on circulating microRNA derived from endothelial cells are discussed as potential biomarkers of atherosclerosis. Specific efforts that promote translational science are encouraged to improve the outcome and prognosis of patients with atherosclerosis.