scholarly journals Mitochondrial DNA Activates NLRP3 Inflammasome and Contributes to Endothelial Dysfunction and Inflammation in Type 1 Diabetic Mice

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Camila André Pereira ◽  
Nathanne Santos Ferreira ◽  
Camila Zillioto Zanotto ◽  
Daniela Carlos ◽  
Rita Tostes
2015 ◽  
Vol 309 (9) ◽  
pp. C593-C599 ◽  
Author(s):  
Ayako Makino ◽  
Anzhi Dai ◽  
Ying Han ◽  
Katia D. Youssef ◽  
Weihua Wang ◽  
...  

Cardiovascular disease is the primary cause of morbidity and mortality in diabetes, and endothelial dysfunction is commonly seen in these patients. Increased O-linked N-acetylglucosamine ( O-GlcNAc) protein modification is one of the central pathogenic features of diabetes. Modification of proteins by O-GlcNAc ( O-GlcNAcylation) is regulated by two key enzymes: β- N-acetylglucosaminidase [ O-GlcNAcase (OGA)], which catalyzes the reduction of protein O-GlcNAcylation, and O-GlcNAc transferase (OGT), which induces O-GlcNAcylation. However, it is not known whether reducing O-GlcNAcylation can improve endothelial dysfunction in diabetes. To examine the effect of endothelium-specific OGA overexpression on protein O-GlcNAcylation and coronary endothelial function in diabetic mice, we generated tetracycline-inducible, endothelium-specific OGA transgenic mice, and induced OGA by doxycycline administration in streptozotocin-induced type 1 diabetic mice. OGA protein expression was significantly decreased in mouse coronary endothelial cells (MCECs) isolated from diabetic mice compared with control MCECs, whereas OGT protein level was markedly increased. The level of protein O-GlcNAcylation was increased in diabetic compared with control mice, and OGA overexpression significantly decreased the level of protein O-GlcNAcylation in MCECs from diabetic mice. Capillary density in the left ventricle and endothelium-dependent relaxation in coronary arteries were significantly decreased in diabetes, while OGA overexpression increased capillary density to the control level and restored endothelium-dependent relaxation without changing endothelium-independent relaxation. We found that connexin 40 could be the potential target of O-GlcNAcylation that regulates the endothelial functions in diabetes. These data suggest that OGA overexpression in endothelial cells improves endothelial function and may have a beneficial effect on coronary vascular complications in diabetes.


2010 ◽  
Vol 13 (6) ◽  
pp. 757-768 ◽  
Author(s):  
Wing Tak Wong ◽  
Xiao Yu Tian ◽  
Aimin Xu ◽  
Chi Fai Ng ◽  
Hung Kay Lee ◽  
...  

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Lei Ying ◽  
Na Li ◽  
Zhengyue He ◽  
Xueqin Zeng ◽  
Yan Nan ◽  
...  

Abstract Endothelial dysfunction initiates and exacerbates hypertension, atherosclerosis and other cardiovascular complications in diabetic mellitus. FGF21 is a hormone that mediates a number of beneficial effects relevant to metabolic disorders and their associated complications. Nevertheless, it remains unclear as to whether FGF21 ameliorates endothelial dysfunction. Therefore, we investigated the effect of FGF21 on endothelial function in both type 1 and type 2 diabetes. We found that FGF21 reduced hyperglycemia and ameliorated insulin resistance in type 2 diabetic mice, an effect that was totally lost in type 1 diabetic mice. However, FGF21 activated AMPKα, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of aorta in both types, suggesting a mechanism that is independent of its glucose-lowering and insulin-sensitizing effects. In vitro, we identified a direct action of FGF21 on endothelial cells of the aorta, in which it bounds to FGF receptors to alleviate impaired endothelial function challenged with high glucose. Furthermore, the CaMKK2-AMPKα signaling pathway was activated to suppress oxidative stress. Apart from its anti-oxidative capacity, FGF21 activated eNOS to dilate the aorta via CaMKK2/AMPKα activation. Our data suggest expanded potential uses of FGF21 for the treatment of vascular diseases in diabetes.


2017 ◽  
Vol 8 ◽  
Author(s):  
Daniela Carlos ◽  
Frederico R. C. Costa ◽  
Camila A. Pereira ◽  
Fernanda A. Rocha ◽  
Juliana N. U. Yaochite ◽  
...  

Diabetes ◽  
2013 ◽  
Vol 62 (11) ◽  
pp. 3839-3850 ◽  
Author(s):  
V. Sudhahar ◽  
N. Urao ◽  
J. Oshikawa ◽  
R. D. McKinney ◽  
R. M. Llanos ◽  
...  

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Anzhi Dai ◽  
Reshma Donthamsetty ◽  
Ying Han ◽  
Brian Scott ◽  
Hong Wang ◽  
...  

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
M Oelze ◽  
S Kröller-Schön ◽  
M Mader ◽  
E Zinßius ◽  
P Stamm ◽  
...  

2014 ◽  
Author(s):  
Sefika Burcak Polat ◽  
Nagihan Ugurlu ◽  
Cenk Sari ◽  
Neslihan Cuhaci ◽  
Reyhan Ersoy ◽  
...  

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