Atheroprotective effects of sphingosine 1-phosphate (S1P) in macrophages and T-cells
Final Report Abstract
Collectively, the experimental results generated in the project unequivocally document for the first time that the amplification of S1P1-dependent signaling in monocytes and macrophages countervails the development of atherosclerotic lesion in a murine model of this disease. The underlying molecular mechanism involves the emergence of a novel macrophage phenotype, in which the parallel activation of the transcription factors PU.1/IRF8 and LXR orchestrates several anti-inflammatory and anti-atherogenic pathways including enhanced secretion of antiinflammatory cytokines, cholesterol disposal and efferocytosis as well as reduced ER stressinduced apoptosis. The results of the project provide a basis for further investigations to elucidate, whether and to which extent the currently identified atheroprotective mechanisms of S1P may contribute to the beneficial effect of this lysosphingolipid on cardiovascular risk inferred from observational studies.
