title: MicroRNA-210 as a novel therapy for treatment of ischemic heart disease.
abstract: BACKGROUND
  MicroRNAs are involved in various critical functions, including the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart.
  
  
  RESULTS
  Using microRNA microarrays, we first showed that microRNA-210 was highly expressed in live mouse HL-1 cardiomyocytes compared with apoptotic cells after 48 hours of hypoxia exposure. We confirmed by polymerase chain reaction that microRNA-210 was robustly induced in these cells. Gain-of-function and loss-of-function approaches were used to investigate microRNA-210 therapeutic potential in vitro. After transduction, microRNA-210 can upregulate several angiogenic factors, inhibit caspase activity, and prevent cell apoptosis compared with control. Afterward, adult FVB mice underwent intramyocardial injections with minicircle vector carrying microRNA-210 precursor, minicircle carrying microRNA-scramble, or sham surgery. At 8 weeks, echocardiography showed a significant improvement of left ventricular fractional shortening in the minicircle vector carrying microRNA-210 precursor group compared with the minicircle carrying microRNA-scramble control. Histological analysis confirmed decreased cellular apoptosis and increased neovascularization. Finally, 2 potential targets of microRNA-210, Efna3 and Ptp1b, involved in angiogenesis and apoptosis were confirmed through additional experimental validation.
  
  
  CONCLUSIONS
  MicroRNA-210 can improve angiogenesis, inhibit apoptosis, and improve cardiac function in a murine model of myocardial infarction. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.
authors.affiliation: Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305-5111, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
authors.forename: Fangjun
authors.initials: F
authors.lastname: Jia
authors.forename: Zhumur
authors.initials: Z
authors.lastname: Ghosh
authors.forename: Maarten A
authors.initials: MA
authors.lastname: Lijkwan
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fasanaro
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D016277:Ventricular Function, Left / Q000235:genetics
chemical_list: C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse