Inhibition of miR-200c Restores Endothelial Function in Diabetic Mice Through Suppression of COX-2
Huina Zhang,Jian Liu,Dan Qu,Li Wang,Jiang-Yun Luo,Chi Wai Lau,Pingsheng Liu,Zhen Gao,George L. Tipoe,Hung Kay Lee,Chi-Fai Ng,Ronald C.W. Ma,Xiaoqiang Yao,Yu Huang +13 more
TLDR
This study demonstrates for the first time to the knowledge that miR-200c is a new mediator of diabetic endothelial dysfunction and inhibition of miR -200c rescues EDRs in diabetic mice, and suggests the potential usefulness ofmiR- 200c as the target for drug intervention against diabetic vascular complications.Abstract:
Endothelial dysfunction plays a crucial role in the development of diabetic vasculopathy. Our initial quantitative PCR results showed an increased miR-200c expression in arteries from diabetic mice and patients with diabetes. However, whether miR-200c is involved in diabetic endothelial dysfunction is unknown. Overexpression of miR-200c impaired endothelium-dependent relaxations (EDRs) in nondiabetic mouse aortas, whereas suppression of miR-200c by anti-miR-200c enhanced EDRs in diabetic db/db mice. miR-200c suppressed ZEB1 expression, and ZEB1 overexpression ameliorated endothelial dysfunction induced by miR-200c or associated with diabetes. More importantly, overexpression of anti-miR-200c or ZEB1 in vivo attenuated miR-200c expression and improved EDRs in db/db mice. Mechanistic study with the use of COX-2(-/-) mice revealed that COX-2 mediated miR-200c-induced endothelial dysfunction and that miR-200c upregulated COX-2 expression in endothelial cells through suppression of ZEB1 and increased production of prostaglandin E2, which also reduced EDR. This study demonstrates for the first time to our knowledge that miR-200c is a new mediator of diabetic endothelial dysfunction and inhibition of miR-200c rescues EDRs in diabetic mice. These new findings suggest the potential usefulness of miR-200c as the target for drug intervention against diabetic vascular complications.read more
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Macro- and microvascular endothelial dysfunction in diabetes
Yi Shi,Paul M. Vanhoutte +1 more
TL;DR: This reviews pays special attention to microRNAs and their modulatory role in diabetes‐induced vascular dysfunction and some therapeutic strategies for preventing and restoring diabetic endothelial dysfunction are highlighted.
Journal ArticleDOI
Oxidative Stress-Induced miR-200c Disrupts the Regulatory Loop Among SIRT1, FOXO1, and eNOS
Fabrizio Carlomosti,Marco D'Agostino,Sara Beji,Alessio Torcinaro,Alessio Torcinaro,Roberto Rizzi,Germana Zaccagnini,Biagina Maimone,Valeria Di Stefano,Francesca De Santa,Sonia Cordisco,Annalisa Antonini,Roberta Ciarapica,Elena Dellambra,Fabio Martelli,Daniele Avitabile,Maurizio C. Capogrossi,Alessandra Magenta +17 more
TL;DR: In vitro results were validated in three in vivo models of oxidative stress, that is, human skin fibroblasts from old donors, femoral arteries from old mice, and a murine model of hindlimb ischemia, and the role of miR-200c on ROS modulation was also investigated.
Journal ArticleDOI
Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs.
Hai-na Zhang,Qiao-qiao Xu,Abhimanyu Thakur,Martin O. Alfred,Manas Chakraborty,Arunima Ghosh,Xuben Yu +6 more
TL;DR: Findings on the role of these non‐coding RNAs in diabetes or hypertension‐associated endothelium dysfunction and the related mechanisms that may pave the way for alleviating endothelial dysfunction and its related complications such as atherosclerosis are discussed.
Journal ArticleDOI
The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy
TL;DR: Novel opinions are presented on “differential influence of ERK1/2 action in cardiac dysfunction, and protection against myocardial ischemia-reperfusion injury”, as well as their relation with the pathogenesis of diabetes and associated complications.
Journal ArticleDOI
Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes.
Eiichiro Satake,Eiichiro Satake,Marcus G. Pezzolesi,Zaipul I. Md Dom,Zaipul I. Md Dom,Adam M. Smiles,Monika A. Niewczas,Monika A. Niewczas,Andrzej S. Krolewski,Andrzej S. Krolewski +9 more
TL;DR: Dysregulation of these miRNAs, which are associated with hyperglycemia in patients with T1D, may contribute to the development of diabetes complications.
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