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Nuclear factor kappa B inhibition improves conductance artery function in type 2 diabetic mice

Authors
 Modar Kassan  ;  Soo-Kyoung Choi  ;  Maria Galán  ;  Mohamed Trebak  ;  Souad Belmadani  ;  Khalid Matrougui 
Citation
 DIABETES-METABOLISM RESEARCH AND REVIEWS, Vol.31(1) : 39-49, 2015 
Journal Title
 DIABETES-METABOLISM RESEARCH AND REVIEWS 
ISSN
 1520-7552 
Issue Date
2015
MeSH
Animals ; Aorta, Thoracic/drug effects ; Aorta, Thoracic/physiopathology ; Arteries/drug effects* ; Arteries/physiology ; Benzamides/pharmacology* ; Cyclohexanones/pharmacology* ; Diabetes Mellitus, Experimental/physiopathology* ; Diabetes Mellitus, Type 2/physiopathology* ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiopathology ; Heart Conduction System/drug effects* ; Heart Conduction System/physiology ; I-kappa B Proteins/pharmacology* ; Male ; Mice ; Mice, Knockout ; NF-kappa B/antagonists & inhibitors* ; Vasodilation/drug effects
Keywords
COX-2 ; NFκB ; PARP-1 ; endothelial function ; thoracic aorta ; type 2 diabetes
Abstract
BACKGROUND: We previously reported that enhanced nuclear factor kappa B (NFκB) activity is responsible for resistance arteries dysfunction in type 2 diabetic mice. METHODS: In this study, we aimed to determine whether augmented NFκB activity also impairs conductance artery (thoracic aorta) function in type 2 diabetic mice. We treated type 2 diabetic (db(-) /db(-) ) and control (db(-) /db(+) ) mice with two NFκB inhibitors (dehydroxymethylepoxyquinomicin, 6 mg/kg, twice a week and IKK-NBD peptide, 500 µg/kg/day) for 4 weeks. RESULTS: As expected, the NFκB inhibition did not affect blood glucose level and body weight. Thoracic aorta vascular endothelium-dependent relaxation (EDR), determined by the wire myograph, was impaired in diabetic mice compared with control and was significantly improved after NFκB inhibition. Interestingly, thoracic EDR was also rescued in db(-) /db(-p50NFκB-/-) and db(-) /db(-PARP-1-/-) double knockout mice compared with db(-) /db(-) mice. Similarly, the acute in vitro down regulation of NFκB-p65 using p65 shRNA lentiviral particles in arteries from db(-) /db(-) mice also improved thoracic aorta EDR. Western blot analysis showed that the p65NFκB phosphorylation, cleaved PARP-1 and COX-2 expression were increased in thoracic aorta from diabetic mice, which were restored after NFκB inhibition and in db(-) /db(-p-50NFκB-/-) and db(-) /db(-PARP-1-/-) mice. CONCLUSIONS: The present results indicate that in male type 2 diabetic mice, the augmented NFκB activity also impairs conductance artery function through PARP-1 and COX-2-dependent mechanisms.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2542/abstract
DOI
10.1002/dmrr.2542
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Choi, Soo Kyoung(최수경) ORCID logo https://orcid.org/0000-0002-7115-6358
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140356
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