Dysregulated Txnip-ROS-Wnt axis contributes to the impaired ischemic heart repair in diabetic mice

Publication date: Available online 24 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mingzhi Shen, Danna Bai, Bei Liu, Xiaozhao Lu, Rongrong Hou, Chao Zeng, Na Li, Zhenhong Fu, Congye Li, Ling Tao, Haichang Wang, Tao YinAbstractHyperglycemia-induced impairment of angiogenesis contributes to the unfavorable prognosis of myocardial ischemia in long-standing diabetes mellitus. The underlying mechanism remains largely unknown and therapeutic strategies thereby limited. In the present study, we investigated the possible involvement of thioredoxin-interacting protein (TXNIP) and Wnt/β-catenin signaling in the context, and their possible relation was also explored. STZ induced diabetic mice were subjected to myocardial infarction (MI). Adenovirus expressing shTXNIP, shCtnnb1 (β-catenin) driven by VE-Cadherin promoter was administered intramyocardially immediately after MI. Cardiac function, histology, and molecular analyses were performed at predetermined time points. Increased endothelial expression of TXNIP was found in diabetic hearts, which correlated well with reduced nuclear β-catenin expression, insufficient angiogenesis, aggravated cardiac remodeling, and poor survival. Endothelial-specific knockdown of TXNIP significantly rescued β-catenin activity, together with increased angiogenesis, preserved cardiac function, and improved survival rate. Moreover, additional knockdown of β-catenin essentially reversed the beneficial...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research