BACKGROUND: Cardiomyocyte apoptosis and inflammation induced by Coxsackievirus B3 (CVB3) are key pathogenetic mechanisms in viral myocarditis. Alterations in microRNAs and lncRNAs are associated with cardiac remodeling. However, whether the microRNA and lncRNA interact to regulate cardiomyocyte apoptosis and inflammation is unknown. METHODS: BALB/c mice were infected with CVB3 to generate acute viral myocarditis model. The expression levels of lncRNA HIF1A-AS1 and miR-138 were examined in mouse myocardium and primary cardiomyocytes with CVB3 infection. We then knocked down HIF1A-AS1 by siRNA and upregulated miR-138 by microRNA mimics in cardiomyocytes. RESULTS: The expression of lncRNA HIF1A-AS1was significantly increased in CVB3-induced myocardium and cardiomyocytes. As documented by flow cytometry, silencing of HIF1A-AS1 alleviated late apoptosis (5.1%±2.8% vs. 17.2%±4.2%, P<0.01) and ROS production (68.73%±2.78% vs. 90.40%±2.86%, P<0.01) compared to their levels in cardiomyocytes transfected with control siRNA. The content of proinflammatory cytokines was substantially decreased by HIF1A-AS1 siRNA. Furthermore, we identified that HIF1A-AS1 bound to miR-138 and significantly suppressed miR-138 expression. Blocking HIF1A-AS1 attenuated IκBα phosphorylation and NF-κB activity, while cotransfection with miR-138 mimics markedly reversed its effect. CONCLUSIONS: In conclusion, lncRNA HIF1A-AS1 promotes NF-κB signaling and subsequently aggravates cardiomyocyte apoptosis and inflammation via targeting miR-138. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: Cardiomyocyte apoptosis and inflammation induced by Coxsackievirus B3 (CVB3) are key pathogenetic mechanisms in viral myocarditis. Alterations in microRNAs and lncRNAs are associated with cardiac remodeling. However, whether the microRNA and lncRNA interact to regulate cardiomyocyte apoptosis and inflammation is unknown. METHODS: BALB/c mice were infected with CVB3 to generate acute viral myocarditis model. The expression levels of lncRNA HIF1A-AS1 and miR-138 were examined in mouse myocardium and primary cardiomyocytes with CVB3 infection. We then knocked down HIF1A-AS1 by siRNA and upregulated miR-138 by microRNA mimics in cardiomyocytes. RESULTS: The expression of lncRNA HIF1A-AS1was significantly increased in CVB3-induced myocardium and cardiomyocytes. As documented by flow cytometry, silencing of HIF1A-AS1 alleviated late apoptosis (5.1%±2.8% vs. 17.2%±4.2%, P<0.01) and ROS production (68.73%±2.78% vs. 90.40%±2.86%, P<0.01) compared to their levels in cardiomyocytes transfected with control siRNA. The content of proinflammatory cytokines was substantially decreased by HIF1A-AS1 siRNA. Furthermore, we identified that HIF1A-AS1 bound to miR-138 and significantly suppressed miR-138 expression. Blocking HIF1A-AS1 attenuated IκBα phosphorylation and NF-κB activity, while cotransfection with miR-138 mimics markedly reversed its effect. CONCLUSIONS: In conclusion, lncRNA HIF1A-AS1 promotes NF-κB signaling and subsequently aggravates cardiomyocyte apoptosis and inflammation via targeting miR-138. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
Authors: Zhejun Cai; Li Shen; Hong Ma; Jin Yang; Du Yang; Han Chen; Jia Wei; Qiulun Lu; Dao Wen Wang; Meixiang Xiang; Jian'an Wang Journal: Circ Heart Fail Date: 2015-05-18 Impact factor: 8.790
Authors: Maarten F Corsten; Ward Heggermont; Anna-Pia Papageorgiou; Sophie Deckx; Aloys Tijsma; Wouter Verhesen; Rick van Leeuwen; Paolo Carai; Hendrik-Jan Thibaut; Kevin Custers; Georg Summer; Mark Hazebroek; Fons Verheyen; Johan Neyts; Blanche Schroen; Stephane Heymans Journal: Eur Heart J Date: 2015-07-22 Impact factor: 29.983
Authors: Alice Weithauser; Peter Bobbert; Silvio Antoniak; Andreas Böhm; Bernhard H Rauch; Karin Klingel; Konstantinos Savvatis; Heyo K Kroemer; Carsten Tschope; Andrea Stroux; Heinz Zeichhardt; Wolfgang Poller; Nigel Mackman; Heinz-Peter Schultheiss; Ursula Rauch Journal: J Am Coll Cardiol Date: 2013-07-17 Impact factor: 24.094