title: Single-Dose Intracardiac Injection of Pro-Regenerative MicroRNAs Improves Cardiac Function After Myocardial Infarction.
abstract: BACKGROUND
  Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application.
  
  
  OBJECTIVE
  As an alternative to the use of viral vectors, we wanted to assess the efficacy of synthetic miRNA mimics in inducing myocardial repair after single intracardiac injection using synthetic lipid formulations.
  
  
  RESULTS
  We comparatively analyzed the efficacy of different lipid formulations in delivering hsa-miR-199a-3p and hsa-miR-590-3p both in primary neonatal mouse cardiomyocytes and in vivo. We established a transfection protocol allowing persistence of these 2 mimics for at least 12 days after a single intracardiac injection, with minimal dispersion to other organs and long-term preservation of miRNA functional activity, as assessed by monitoring the expression of 2 mRNA targets. Administration of this synthetic formulation immediately after myocardial infarction in mice resulted in marked reduction of infarct size and persistent recovery of cardiac function.
  
  
  CONCLUSIONS
  A single administration of synthetic miRNA-lipid formulations is sufficient to stimulate cardiac repair and restoration of cardiac function.
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.).
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Lesizza
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.).
authors.forename: Giulia
authors.initials: G
authors.lastname: Prosdocimo
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.).
authors.forename: Valentina
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.).
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Sinagra
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.).
authors.forename: Serena
authors.initials: S
authors.lastname: Zacchigna
authors.affiliation: From the Molecular Medicine (P.L., G.P., V.M., M.G.) and Cardiovascular Biology (S.Z.) Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; and Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (P.L., G.S., S.Z., M.G.). giacca@icgeb.org.
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D007267:Injections; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D020127:Recovery of Function; D012038:Regeneration; D013997:Time Factors; D014162:Transfection; D016277:Ventricular Function, Left
chemical_list: D035683:MicroRNAs
keywords: microRNA; myocardial infarction; regeneration; therapy; transfection