Cell type-specific localization of human cardiac S1P receptors

Sphingosine 1-phosphate (S1P), which derives from the metabolism of sphingomyelin, is mainly synthesized, stored, and released from platelets after activation by physiological and pathophysiological events. S1P acts in cardiovascular tissues through cell surface G-protein-coupled receptors of the endothelial differentiation gene (EDG) family, i.e., EDG1, EDG3 and EDG5. The aim of the present study was to assess the precise distribution of EDG1, EDG3, and EDG5 receptors expressed in human cardiovascular tissues to investigate their respective physiological implication. When assessed by Northern blots, EDG1, EDG3, and EDG5 displayed wide expression levels in decreasing order, respectively. In particular, EDG3 was mainly detected in the aorta. Detailed analysis by in situ hybridization (ISH) and immunohistochemistry (IHC) revealed strong EDG1 expression in cardiomyocytes and in endothelial cells of cardiac vessels. In cardiomyocytes, the EDG1 receptor is likely to be co-expressed with EDG3 and EDG5, although EDG1 exhibits the most prominent expression pattern. Unlike EDG3 and EDG5, which are expressed in the smooth muscle cell layer of the human aorta, no signal corresponding to EDG1 expression could be detected in the aorta. Moreover, only EDG3 expression was also found in smooth muscle cells of cardiac vessels. The present results provide new insight into the expression pattern of S1P receptors in human cardiovascular tissues, indicating a differential pattern of expression for these receptors in human vessels.