title: Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction.
abstract: Dicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer depletion in adult mice.
  
  
  
  Conditional Dicer deletion in the adult murine myocardium demonstrated compromised heart function, mitochondrial dysfunction and oxidant stress. Elevated miR-15b was observed as an early response to Dicer depletion and was found to silence Pim-1 kinase, a protein responsible for maintaining mitochondrial integrity and function. Anti-miRNA based suppression of induced miRNA-15b rescued the function of Dicer-depleted adult heart and attenuated hypertrophy.
  
  
  
  Anti-miRNA based suppression of inducible miRNA-15b can prevent rapid loss of cardiac function in a Dicer-depleted adult heart and can be a key approach worthy of therapeutic consideration.
authors.affiliation: Davis Heart and Lung Research Institute and Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio, United States of America.
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Jaideep
authors.initials: J
authors.lastname: Banerjee
authors.forename: Surya C
authors.initials: SC
authors.lastname: Gnyawali
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
authors.forename: Douglas
authors.initials: D
authors.lastname: Pfeiffer
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004195:Disease Models, Animal; D004452:Echocardiography; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000235:genetics / Q000503:physiopathology*; D006334:Heart Function Tests; D008279:Magnetic Resonance Imaging; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C570833:Mirn15 microRNA, mouse; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases