BACKGROUND: @entity731 is a major cause of mortality in @entity1 with @entity6 . However, novel breakthrough therapies have yet to be approved in this setting. @entity10783 -isomerase-1 ( @entity41543 ) is emerging as a key molecule implicated in vascular oxidative stress and @entity32 . In the present study, we investigate whether pharmacological inhibition of @entity41543 may protect against @entity6 -induced oxidative stress, @entity409 and @entity32 . METHODS AND RESULTS: Experiments were performed in @entity1 aortic endothelial cells (HAECs) exposed to normal (5mmol/L) or high glucose (25mmol/L) concentrations, in the presence of @entity41543 inhibitor @entity57276 (10 M) or vehicle (<1% @entity1068 ). In parallel, @entity3839 -induced @entity6 @entity19 were treated with @entity57276 i.p. every other day for 30days (1mg/Kg). Organ chamber experiments were performed in aortic rings to assess endothelium-dependent relaxations to @entity934 ( @entity3451 10(-9) to 10(-6)mol/L). Mitochondrial oxidative stress, organelle integrity as well as NF-kB-dependent inflammatory signatures were determined both in HAECs and aortas from @entity6 @entity19 . In HAECs, ambient @entity4854 increased mitochondrial @entity224 anion generation while treatment with @entity57276 prevented this phenomenon. Pharmacological inhibition of @entity41543 also preserved mitochondrial integrity, @entity842 availability and endothelial expression of adhesion molecules. Interestingly enough, @entity409 , oxidative stress and NF-kB-driven @entity32 were significantly attenuated in @entity6 @entity19 chronically treated with @entity57276 as compared to vehicle-treated animals. CONCLUSION: Pharmacological inhibition of @entity41543 by @entity57276 prevents @entity4854 -induced @entity455 . Taken together, our findings may set the stage for novel therapeutic approaches to prevent @entity455 in @entity1 with @entity6 .

XXXX inhibitor @entity57276 prevents diabetic vascular dysfunction.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['vascular inflammation', 'inflammation'] @entity455 :: ('MESH:D014652', 'Disease') :: ['vascular complications', 'vascular dysfunction'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetes'] @entity57276 :: ('MESH:C005134', 'Chemical') :: ['Juglone'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity3451 :: ('D000109', 'Chemical') :: ['Ach'] @entity409 :: ('MESH:D008107', 'Disease') :: ['endothelial dysfunction'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozotocin'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity41543 :: ('5300', 'Gene') :: ['Pin1'] @entity10783 :: ('CHEBI:26274', 'Chemical') :: ['Prolyl'] @entity731 :: ('MESH:D050197', 'Disease') :: ['Atherosclerosis'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol'] @entity4854 :: ('MESH:D006943', 'Disease') :: ['hyperglycemia'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity41543 :: (5300,Gene) :: ['Pin1']
