Sphingosine-1-Phosphate in the Regulation of Vascular Tone: A Finely Tuned Integration System of SIP Sources, Receptors, and Vascular Responsiveness

摘要

Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid that plays an important role in the physiology of the cardiovascular, nervous and immune systems. Red blood cells are the major source of plasma S1P, where it mainly associates with High-density lipoproteins (HDL). There is a steep concentration gradient of S1P between plasma and the interstitial compartment, with S1P being present in the low micromolar range in plasma and at least 1 order of magnitude lower in the interstitial fluid. S1P exerts numerous effects on the vascular cells regulating arterial tone-the smooth muscle cell and the endothelial cell-via a set of 5 cognate G protein-coupled receptors (S1P_(1 to 5)) expressed differentially in the different cell types. In addition, S1P has negative effects on cardiac rate, contractility, and output. All of this makes S1P a candidate for a bona fide modulator of vascular tone.