Cardiac-specific suppression of NF-kappa B signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system

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dc.contributor.author Thomas, Candice M.
dc.contributor.author Yong, Qian Chen
dc.contributor.author Rosa, Rodolfo M. [UNIFESP]
dc.contributor.author Seqqat, Rachid
dc.contributor.author Gopal, Shanthi
dc.contributor.author Casarini, Dulce E. [UNIFESP]
dc.contributor.author Jones, W. Keith
dc.contributor.author Gupta, Sudhiranjan
dc.contributor.author Baker, Kenneth M.
dc.contributor.author Kumar, Rajesh
dc.date.accessioned 2016-01-24T14:37:53Z
dc.date.available 2016-01-24T14:37:53Z
dc.date.issued 2014-10-01
dc.identifier http://dx.doi.org/10.1152/ajpheart.00340.2014
dc.identifier.citation American Journal of Physiology-heart and Circulatory Physiology. Bethesda: Amer Physiological Soc, v. 307, n. 7, p. H1036-H1045, 2014.
dc.identifier.issn 0363-6135
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/38241
dc.description.abstract Activation of NF-kappa B signaling in the heart may be protective or deleterious depending on the pathological context. in diabetes, the role of NF-kappa B in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-kappa B modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated I kappa B-alpha in the heart (3M mice), which prevented activation of canonical NF-kappa B signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. in contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. in diabetic WT mice, an increase in the phospholamban/sarco(endo) plasmic reticulum Ca2+-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca2+ handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. in conclusion, these results demonstrate that inhibition of NF-kappa B signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca2+ handling and inhibition of the cardiac renin-angiotensin system. en
dc.description.sponsorship National Heart, Lung, and Blood Institute
dc.format.extent H1036-H1045
dc.language.iso eng
dc.publisher Amer Physiological Soc
dc.relation.ispartof American Journal of Physiology-heart and Circulatory Physiology
dc.rights Acesso aberto
dc.subject nuclear factor-kappa B en
dc.subject renin-angiotensin system en
dc.subject diabetic cardiomyopathy en
dc.subject I kappa B-alpha transgenic mice en
dc.title Cardiac-specific suppression of NF-kappa B signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system en
dc.type Artigo
dc.contributor.institution Texas A&M Hlth Sci Ctr
dc.contributor.institution Baylor Scott & White Hlth
dc.contributor.institution Cent Texas Vet Hlth Care Syst
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Loyola Univ Chicago
dc.description.affiliation Texas A&M Hlth Sci Ctr, Div Mol Cardiol, Dept Med, Coll Med, Temple, TX USA
dc.description.affiliation Baylor Scott & White Hlth, Temple, TX USA
dc.description.affiliation Cent Texas Vet Hlth Care Syst, Temple, TX USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.affiliation Loyola Univ Chicago, Maywood, IL USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.sponsorshipID National Heart, Lung, and Blood Institute: 5-R01-HL-090817
dc.identifier.doi 10.1152/ajpheart.00340.2014
dc.description.source Web of Science
dc.identifier.wos WOS:000343239800011



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