Since the synergistic effects are significantly higher in AVICs from stenotic than control valves and lower in PVIC, and can be blocked with S1P receptor and TLR4 antagonists, the S1P receptors-TLR4 interplay might have potential long-term pathophysiologically relevant consequences and offers new molecular targets for aortic stenosis treatment. This evidence concerns the gene TLR4 and aortic stenosis.