Cell Type-specific Localization of Human Cardiac S1P Receptors

Abstract

S U M M A R Y 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.

Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects

“…Studies have shown that S1P1 is highly expressed in atrial, septal and ventricular cardiomyocytes, and in the endothelial cells of cardiac vessels in humans [4,5]. Furthermore, S1P1 is considered to …”

“…The study period was a maximum of 44 days for each subject, comprising a 21-day screening period, a 12-day treatment period (days [1][2][3][4][5][6][7][8][9][10][11][12] and an end of study assessment 10 days after the last treatment day (day 22). Sub-E. Legangneux et al…”

Sphingosine 1-Phosphate (S1P) Receptor Subtypes S1P1 and S1P3, Respectively, Regulate Lymphocyte Recirculation and Heart Rate

“…The demonstration in vivo that a non-selective S1P receptor agonist active on S1P 3 induces bradycardia in wildtype mice that is abolished in S1P 3 Ϫ/Ϫ mice provides further support for the role of S1P 3 in the heart. Both S1P 1 and S1P 3 are expressed on cardiac endothelium and perhaps myocardium (42), yet deletion of S1P 3 alone abolishes the bradycardia induced by non-selective S1P receptor agonists, and an S1P 1 -selective agonist does not induce bradycardia. These data provide evidence that the pleiotropicity of S1P function has, at least in the specific instances of lymphocyte recirculation and bradycardia, a basis in differential receptor subtype usage in the cardiac and lymphatic systems, respectively.…”

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

“…Further, S1PþJTE013 treatment resulted in a significant expansion in venules relative to all comparative treatments, including FTY720. This discrepancy in arterial and venous responses to the same compound could be explained by differences in receptor expression patterns between the two vessel types, 35,36 but further validation is required. Unexpectedly, S1PþJTE013 delivery did not significantly increase functional length density; in fact, length density significantly decreased over the course of 7 days compared to FTY720 treatment, although not statistically different than treatment with S1P alone.…”