5-hydroxytryptamine in the cardiovascular system: focus on the serotonin transporter (SERT).

1. The function of the serotonin transporter (SERT) is to take up and release serotonin (5-hydroxytyptamine (5-HT)) from cells and this function of SERT in the central nervous system (CNS) is well-documented; SERT is the target of selective serotonin reuptake inhibitors used in the treatment of CNS disorders, such as depression. 2. The aim of the present review is to discuss our current knowledge of 5-HT and SERT in the cardiovascular (CV) system, as well as their function in physiological and pathophysiological states. 3. The SERT protein has been located in multiple CV tissues, including the heart, blood vessels, brain, platelets, adrenal gland and kidney. Modification of SERT function occurs at both transcriptional and translational levels. The functions of SERT in these tissues is largely unexplored, but includes modulation of cardiac and smooth muscle contractility, platelet aggregation, cellular mitogenesis, modulating neuronal activity and urinary excretion. 4. Recent studies have uncovered potential relationships between the expression of SERT gene promoter variants (long (l) or short (s)) with CV diseases. Specifically, the risk of myocardial infarction and pulmonary hypertension is increased with expression of the ll promoter, a variant associated with increased expression and function of SERT. The relationship between promoter variants and other CV diseases has not been investigated. 5. Newly available experimental tools, such as pharmacological compounds and genetically altered mice, should prove useful in the investigation of the function of SERT in the CV system. 6. In summary, the function of SERT in the CV system is just beginning to be revealed.