title: Single intracoronary injection of encapsulated antagomir-92a promotes angiogenesis and prevents adverse infarct remodeling.
abstract: BACKGROUND
  Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction
  Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects.
  
  
  RESULTS
  In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 μm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall-motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2).
  
  
  CONCLUSIONS
  Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.
authors.affiliation: Laboratory of Experimental and Molecular Cardiocirculatory Pathology, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., I.B., A.R.S., D.G.D.) Department of Cardiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., T.G.A., J.R., B.G.B., D.G.D.).
authors.forename: Neus
authors.initials: N
authors.lastname: Bellera
authors.affiliation: Laboratory of Experimental and Molecular Cardiocirculatory Pathology, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., I.B., A.R.S., D.G.D.).
authors.forename: Ignasi
authors.initials: I
authors.lastname: Barba
authors.affiliation: Laboratory of Experimental and Molecular Cardiocirculatory Pathology, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., I.B., A.R.S., D.G.D.).
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodriguez-Sinovas
authors.affiliation: I+D Pierre-Fabre Ibérica S.A., Cerdanyola del Vallès, Spain (E.F., M.A.A., A.).
authors.forename: Eulalia
authors.initials: E
authors.lastname: Ferret
authors.affiliation: I+D Pierre-Fabre Ibérica S.A., Cerdanyola del Vallès, Spain (E.F., M.A.A., A.).
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Asín
authors.affiliation: Department of Cardiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., T.G.A., J.R., B.G.B., D.G.D.).
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Gonzalez-Alujas
authors.affiliation: Department of Cardiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., T.G.A., J.R., B.G.B., D.G.D.).
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Rodon
authors.affiliation: Department of Animal Housing, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (M.E., C.F.).
authors.forename: Marielle
authors.initials: M
authors.lastname: Esteves
authors.affiliation: Department of Animal Housing, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (M.E., C.F.).
authors.forename: Carla
authors.initials: C
authors.lastname: Fonseca
authors.affiliation: Department of Anatomical Pathology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.T.).
authors.forename: Nuria
authors.initials: N
authors.lastname: Toran
authors.affiliation: Department of Cardiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., T.G.A., J.R., B.G.B., D.G.D.).
authors.forename: Bruno
authors.initials: B
authors.lastname: Garcia Del Blanco
authors.affiliation: I+D Pierre-Fabre Ibérica S.A., Cerdanyola del Vallès, Spain (E.F., M.A.A., A.).
authors.forename: Amadeo
authors.initials: A
authors.lastname: Pérez
authors.affiliation: Laboratory of Experimental and Molecular Cardiocirculatory Pathology, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., I.B., A.R.S., D.G.D.) Department of Cardiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain (N.B., T.G.A., J.R., B.G.B., D.G.D.).
authors.forename: David
authors.initials: D
authors.lastname: Garcia-Dorado
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007267:Injections; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008863:Microspheres; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion; D018919:Neovascularization, Physiologic; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D020127:Recovery of Function; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides
keywords: Angiogenesis; antagomir; heart failure; microRNA; myocardial infarction; remodeling