S1PR1 and rheumatoid arthritis: Because soluble VE-cadherin has been shown to correlate with disease activity in RA (33, 47), we considered the possibility that VE-cadherin is shed by a metalloproteinase(s) during SIA and that S1PR1-ECKO mice have increased arthritis, at least in part, because of enhanced shedding of VE-cadherin in the synovial microvasculature.