Sphingosine-1-phosphate receptor 4 (S1P4) deficiency does not alter Th2-induced pulmonary vascular hyperresponsiveness

Introduction: Pulmonary arterial hypertension (PAH) is characterized by increased vasoconstriction and pulmonary arterial remodeling leading to elevated pulmonary vascular resistance and right ventricular failure. Pulmonary Th2 inflammation induces morphologic and functional changes resembling PAH. Sphingosine-1-phosphate (S1P) signals via five G protein-coupled receptors (S1P1 – 5) thereby regulating a wide range of immune and vascular functions. In the lung, S1P is predominantly synthetized by sphingosine kinase 1 (SphK1), which has been shown to modulate pulmonary vascular hyperresponsiveness. The role of S1P…