Thus far, our work provides ample evidence that sphingosine-1-phosphate (S1P) and its signaling axis play a key role in immune cell recruitment, cytokine production and vascular tone regulation during experimental hypertension, heart failure and stroke. Recently, we described a novel role for the S1P generating enzyme SphK2 in the pathogenesis of experimental hypertension, whereby hematopoietic SphK2 activity crucially regulates plasma S1P levels and thus, the T-cell-mediated elevation of blood pressure. These findings bear strong translational potential as elevated plasma S1P levels and inflammation have been reported in different types of hypertension in patients. Because hypertension is a major contributor to organ failure by promoting vascular dysfunction, dissecting novel therapeutic targets to effectively improve such complications is of vital importance. In respect to our findings thus far, we believe that the S1P signaling axis will emerge as attractive therapeutic tool.

Cardiovascular disease such as heart attack, stroke, and peripheral vascular disease, is the number-one health problem in the world. Despite remarkable progress in diagnosis and prevention, cardiovascular diseases cause disability and death at an astounding rate. The best opportunity to develop and implement new strategies for preventing and treating cardiovascular disease lies in the understanding of its underlying mechanisms. Our research therefore aims to isolate novel therapeutic targets that effectively prevent and most importantly, also reverse complications mediated by cardiovascular risk factors such as hypertension. Specifically, we are interested in understanding of sphingosine-1-phosphate (S1P) signaling and its role in the regulation of the vascular and the immune system during hypertension, heart failure, stroke and cerebral small vessel disease.