Roles of Serotonin in Atherothrombosis and Related Diseases

Serotonin (5-hydroxytryptamine, 5-HT) was first identified as a powerful vasoconstrictor over a century ago (Rapport et al., 1948), and in the past 20 years has been recognized as an arterial smooth muscle mitogen (Nemecek et al., 1986). Serotonin is also known to act as a monoaminergic neurotransmitter in the brain and gastrointestinal tract, and is involved in a variety of functions, such as mood regulation, urine storage and voiding, the regulation of sleep and body temperature, food intake, and intestinal motility (Ni & Watts, 2006). Serotonin is predominantly synthesized and secreted into the blood stream by enterochromaffin cells in the gastrointestinal tract and is rapidly taken up and stored in small dense granules in platelets (Fanburg & Lee, 1997). In humans, 90% of the body’s 5-HT is located in the intestines, and the rest is present primarily in platelets (89%) and the central nervous system (12%) (Fanburg & Lee, 1997). When platelets adhere and aggregate at sites of vessel injury, 5-HT is secreted and directly accelerates platelet aggregation (De Clerck, 1990; Wester et al., 1992).