Hong-Jun Zhu1, De-Guo Wang2, Ji Yan1, Jian Xu1. 1. Department of Cardiology, Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei 230001, China. 2. Department of Gerontology, Yijishan Hospital of Wannan Medical College Wuhu 241001, China.
Abstract
BACKGROUND AND AIMS: The heart in diabetic state is sensitive to myocardial ischemia reperfusion (mI/R) injury. In the present study, we investigated the potential mechanisms of modulating mI/R injury in diabetic state. METHODS: Diabetic db/db mice and control non-diabetic mice were administrated with mI/R injury or sham operation. Mouse atrial-derived cardiac cell line HL-1 subjected to hypoxia-reoxygenation (H/R) was used as in vitro model of I/R injury to the heart. RESULTS: Compared with normal mice, mI/R elevated the levels of myocardial infarct size, apoptosis and TXNIP expression (in mRNA and protein) in diabetic mice. Myocardial miR-135a expression level was reduced in diabetic mice regardless of mI/R treatment or not. MiR-135a overexpression protected myocardial cells from mI/R injury in diabetic mice. In vitro, high glucose incubation contributed to a significant down-regulation of miR-135a and up-regulation of TXNIP in cells with or without H/R treatment. Luciferase reporter assay showed that TXNIP was a target gene of miR-135a. MiR-135a overexpression protected HL-1 cells from H/R injury in high glucose condition, while this effect was reversed by up-regulated TXNIP. CONCLUSION: miR-135a protects against mI/R injury by decreasing TXNIP expression in diabetic state.
BACKGROUND AND AIMS: The heart in diabetic state is sensitive to myocardial ischemia reperfusion (mI/R) injury. In the present study, we investigated the potential mechanisms of modulating mI/R injury in diabetic state. METHODS:Diabetic db/db mice and control non-diabeticmice were administrated with mI/R injury or sham operation. Mouse atrial-derived cardiac cell line HL-1 subjected to hypoxia-reoxygenation (H/R) was used as in vitro model of I/R injury to the heart. RESULTS: Compared with normal mice, mI/R elevated the levels of myocardial infarct size, apoptosis and TXNIP expression (in mRNA and protein) in diabeticmice. Myocardial miR-135a expression level was reduced in diabeticmice regardless of mI/R treatment or not. MiR-135a overexpression protected myocardial cells from mI/R injury in diabeticmice. In vitro, high glucose incubation contributed to a significant down-regulation of miR-135a and up-regulation of TXNIP in cells with or without H/R treatment. Luciferase reporter assay showed that TXNIP was a target gene of miR-135a. MiR-135a overexpression protected HL-1 cells from H/R injury in high glucose condition, while this effect was reversed by up-regulated TXNIP. CONCLUSION:miR-135a protects against mI/R injury by decreasing TXNIP expression in diabetic state.
Authors: Steffen U Eisenhardt; Jakob B W Weiss; Christian Smolka; Johanna Maxeiner; Franziska Pankratz; Xavier Bemtgen; Max Kustermann; Jan R Thiele; Yvonne Schmidt; G Bjoern Stark; Martin Moser; Christoph Bode; Sebastian Grundmann Journal: Basic Res Cardiol Date: 2015-04-28 Impact factor: 17.165
Authors: Richard Engbersen; Niels P Riksen; Marc J Mol; Bert Bravenboer; Otto C Boerman; Patrick Meijer; Wim J G Oyen; Cees Tack; Gerard A Rongen; Paul Smits Journal: Cardiovasc Diabetol Date: 2012-10-10 Impact factor: 9.951