ORAI and stromal interaction molecule (STIM) are store-operated channel molecules that play essential roles in @entity1 physiology through a coupling mechanism of internal @entity141 store to @entity141 influx. However, the roles of ORAI and STIM in vascular endothelial cells under @entity6 conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high @entity413 or hyperglycaemia using in vitro cell models, in vivo @entity6 @entity19 and tissues from @entity1 . We found that @entity7011 -3 and @entity7010 -2 were ubiquitously expressed in @entity1 vasculatures. Their expression was upregulated by chronic treatment with high @entity413 (HG, 25  mM @entity413 ), which was accompanied by enhanced store-operated @entity141 influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita @entity6 @entity19 (C57BL/6- @entity15979 ) and @entity3839 -induced @entity6 @entity19 , and aortae from @entity6 @entity1 . HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor @entity205 and @entity9890 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor @entity65779 prevented the gene upregulation in Akita @entity19 . However, HG had no direct effects on @entity7011 -3 currents and the channel activation process through cytosolic @entity7010 movement in the cells co-expressing @entity7010 -EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through @entity141 -calcineurin-NFAT pathway is a novel mechanism causing abnormal @entity141 homeostasis and @entity409 under hyperglycaemia. KEY MESSAGE: @entity7011 -3 and @entity7010 -2 are ubiquitously expressed in vasculatures and upregulated by high @entity413 . Increased expression is confirmed in Akita ( @entity15979 ) and STZ @entity6 @entity19 and @entity1 . Upregulation mechanism is mediated by @entity141 /calcineurin/ @entity9890 signalling. High @entity413 has no direct effects on @entity7011 -3 channel activity and channel activation process.

High XXXX enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic'] @entity7010 :: ('6786', 'Gene') :: ['STIM1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity409 :: ('MESH:D008107', 'Disease') :: ['endothelial dysfunction'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozocin'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin A'] @entity7011 :: ('84876', 'Gene') :: ['ORAI1'] @entity65779 :: ('MESH:C494244', 'Chemical') :: ['A-285222'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity15979 :: ('16334(Tax:10090)', 'Gene') :: ['Ins2(Akita)/J'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose', 'D-glucose'] @entity9890 :: ('4775', 'Gene') :: ['NFATc3']
@entity413 :: (MESH:D005947,Chemical) :: ['glucose']
