title: MicroRNA-208a Dysregulates Apoptosis Genes Expression and Promotes Cardiomyocyte Apoptosis during Ischemia and Its Silencing Improves Cardiac Function after Myocardial Infarction.
abstract: OBJECTIVE
  miR-208a is associated with adverse outcomes in several cardiac pathologies known to have increased apoptosis, including myocardial infarction (MI). We investigated if miR-208a has proapoptotic effects on ischemic cardiomyocytes and if its silencing has therapeutic benefits in MI.
  
  
  RESULTS
  The effect of miR-208a on apoptosis during ischemia was studied in cultured neonatal mice myocytes transfected with agomir or antagomir. Differential gene expression was assessed using microarrays. MI was induced in male C57BL/6 mice randomly assigned to antagomir (n = 6) or control group (n = 7), while sham group (n = 7) had sham operation done. Antagomir group received miR208a antagomir, while control and sham group mice received vehicle only. At 7 and 28 days, echocardiography was done and thereafter hearts were harvested for analysis of apoptosis by TUNEL method, fibrosis using Masson's trichrome, and hypertrophy using hematoxylin and eosin. miR-208a altered apoptosis genes expression and increased apoptosis in ischemic cardiomyocytes. Therapeutic inhibition of miR-208a decreased cardiac fibrosis, hypertrophy, and apoptosis and significantly improved cardiac function 28 days after MI.
  
  
  CONCLUSIONS
  miR-208a alters apoptosis genes expression and promotes apoptosis in ischemic cardiomyocytes, and its silencing attenuates apoptosis, fibrosis, and hypertrophy after MI, with significant improvement in cardiac function.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, China.
authors.forename: Hasahya
authors.initials: H
authors.lastname: Tony
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Meng
authors.affiliation: Department of Cardiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, China.
authors.forename: Aijia
authors.initials: A
authors.lastname: Yu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, China.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, China.
authors.forename: Kunwu
authors.initials: K
authors.lastname: Yu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-Fang Avenue, Wuhan 430022, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005355:Fibrosis; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*
chemical_list: C550906:MIRN208 microRNA, human; D035683:MicroRNAs