Yansong Wang1, Yanan Jiang2, Xi Sun3, Xiuyun Shen4, Hui Wang5, Chaorun Dong6, Baojiang Lu7, Yan Yan8, Yuan Lu9, Moyondafoluwa Blessing Fasae10, Bing Liu11, Yunlong Bai12. 1. Department of Pain Management, Qunli Branch, The First Affiliated Hospital of Harbin Medical University, Harbin 150070, PR China; Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: wangyansong_1509@hotmail.com. 2. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150086, PR China; College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, PR China. Electronic address: jiangyanan@hrbmu.edu.cn. 3. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: sunxi1005@outlook.com. 4. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: xiuyunshen2018@163.com. 5. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: wangh08@outlook.com. 6. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: dongchaorun0604@126.com. 7. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: lvbaojianghmu@163.com. 8. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: yy409091992@163.com. 9. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: YuanLvHRB@163.com. 10. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China. Electronic address: yondafasae@gmail.com. 11. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150086, PR China. Electronic address: liubingdoctor123@126.com. 12. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150086, PR China. Electronic address: baiyunlong@ems.hrbmu.edu.cn.
Abstract
BACKGROUND/AIMS: Acute myocardial infarction (AMI) is a major clinical manifestation of ischemic heart disease and represents a significant cause of morbidity and mortality. However, key regulators in the pathogenesis of ischemic heart disease remain controversial. The present study was designed to investigate the involvement of miR-200a and its related mechanism in AMI. METHODS: Left coronary artery (LCA) ligation was conducted to induce an AMI mouse model. The infarct size was measured by TTC staining. H2O2 was used to induce an AMI model in vitro. miR-200a mimics, anti-miR-200a antisense oligodeoxyribonucleotides (AMO-200a), as well as corresponding negative controls were transfected into cardiomyocytes to observe the effect of miR-200a. Flow cytometry was used to detect cell apoptosis. Real-time PCR, immunofluorescence and western blot assays were used to evaluate gene expression at RNA or protein levels, respectively. RESULTS: Apoptosis was activated in AMI models. The expression of miR-200a was upregulated both in the peri-infarcted region of mice myocardium and H2O2-treated cardiomyocytes. The co-administration of AMO-200a decreased the number of apoptosis cells and altered the expression of apoptosis related proteins. Interestingly, bioinformatics analysis results revealed that miR-200a could bind to the 3'-untranslated regions (3'-UTR) of Fus mRNA. In addition, the expression of Fus was downregulated in the AMI mouse models and in H2O2-treated cardiomyocytes. The alteration of miR-200a negatively regulated Fus expression in cardiomyocytes. Also, the protective effect of AMO-200a was observed through its regulation of Fus. CONCLUSION: MiR-200a-dependent apoptosis signaling pathway plays an important role in the pathogenesis of AMI injury and could be an exciting potential therapeutic target.
BACKGROUND/AIMS: Acute myocardial infarction (AMI) is a major clinical manifestation of ischemic heart disease and represents a significant cause of morbidity and mortality. However, key regulators in the pathogenesis of ischemic heart disease remain controversial. The present study was designed to investigate the involvement of miR-200a and its related mechanism in AMI. METHODS: Left coronary artery (LCA) ligation was conducted to induce an AMI mouse model. The infarct size was measured by TTC staining. H2O2 was used to induce an AMI model in vitro. miR-200a mimics, anti-miR-200a antisense oligodeoxyribonucleotides (AMO-200a), as well as corresponding negative controls were transfected into cardiomyocytes to observe the effect of miR-200a. Flow cytometry was used to detect cell apoptosis. Real-time PCR, immunofluorescence and western blot assays were used to evaluate gene expression at RNA or protein levels, respectively. RESULTS: Apoptosis was activated in AMI models. The expression of miR-200a was upregulated both in the peri-infarcted region of mice myocardium and H2O2-treated cardiomyocytes. The co-administration of AMO-200a decreased the number of apoptosis cells and altered the expression of apoptosis related proteins. Interestingly, bioinformatics analysis results revealed that miR-200a could bind to the 3'-untranslated regions (3'-UTR) of Fus mRNA. In addition, the expression of Fus was downregulated in the AMI mouse models and in H2O2-treated cardiomyocytes. The alteration of miR-200a negatively regulated Fus expression in cardiomyocytes. Also, the protective effect of AMO-200a was observed through its regulation of Fus. CONCLUSION:MiR-200a-dependent apoptosis signaling pathway plays an important role in the pathogenesis of AMI injury and could be an exciting potential therapeutic target.
Authors: Eleanor L Schuchardt; Shelley D Miyamoto; Timothy Crombleholme; Anis Karimpour-Fard; Armin Korst; Bonnie Neltner; Lisa W Howley; Bettina Cuneo; Carmen C Sucharov Journal: J Cardiovasc Dev Dis Date: 2022-01-23