title: Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice.
abstract: Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Innovative Drug Research Center of Shanghai University, Shanghai, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Huang
authors.affiliation: Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Innovative Drug Research Center of Shanghai University, Shanghai, China.
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Innovative Drug Research Center of Shanghai University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Genomics & Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiuchang
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Kong
authors.affiliation: Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.|Innovative Drug Research Center of Shanghai University, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao