BACKGROUND: Epidemiological data strongly indicate that @entity6 increases the incidence of @entity712 . Although the benefit of angiotensin-converting enzyme inhibitor (ACE-I) treatment during and after @entity583 has been found to be greater in diabetics than nondiabetics and activation of the renin-angiotensin system (RAS) has been implicated, the molecular basis of these actions remains unclear. METHODS AND RESULTS: We generated @entity19 with cardiac-specific overexpression of wild-type p90 ribosomal S6 kinase (WT- @entity70523 -Tg) and a dominant-negative form of @entity70523 ( @entity70523 ). Recovery of cardiac function after @entity63 /reperfusion in WT- @entity70523 -Tg isolated @entity19 hearts was significantly impaired. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed specific induction of prorenin-converting enzyme (PRECE) in WT- @entity70523 -Tg @entity19 . mRNA induction of PRECE was confirmed with serial angiotensinogen protein reduction after perfusion in WT- @entity70523 -Tg @entity19 , suggesting an increase of angiotensinogen cleavage and subsequent RAS activation in WT- @entity70523 -Tg @entity19 . We investigated the role of the RAS in WT- @entity70523 -Tg animals after @entity63 /reperfusion with the use of an ACE-I ( @entity3371 ) and an angiotensin II type 1 receptor blocker ( @entity9885 ). We did not observe any effect of these inhibitors in non-Tg littermate controls, thus corroborating other reports in rodents. In contrast, both @entity3371 and @entity9885 significantly improved cardiac function and reduced @entity1188 size in WT- @entity70523 -Tg @entity19 . At 8 months of age, WT- @entity70523 -Tg @entity19 developed @entity299 . @entity70523 activity and PRECE mRNA were both increased by @entity3839 -induced @entity4854 in non-Tg littermate controls, whereas @entity70523 animals exposed to @entity3839 did not have PRECE induction. CONCLUSIONS: This study demonstrates the critical role of @entity70523 in @entity4854 -mediated myocardial PRECE induction, which may explain the augmentation of the RAS in @entity6 hearts and provide an alternative therapeutic approach to treat @entity13088 .

Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in @entity63 and XXXX .

@entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity70523 :: ('20112(Tax:10090)', 'Gene') :: ['DN-p90RSK-Tg', 'p90RSK'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetes'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'transgenic mice'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity13088 :: ('MESH:D058065', 'Disease') :: ['diabetic cardiomyopathy'] @entity3371 :: ('CHEBI:3380', 'Chemical') :: ['captopril'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozotocin'] @entity9885 :: ('MESH:C437965', 'Chemical') :: ['olmesartan'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac dysfunction'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction'] @entity4854 :: ('MESH:D006943', 'Disease') :: ['hyperglycemia']
@entity6 :: (MESH:D003920,Disease) :: ['diabetic myocardium']
