title: Evolving targeted therapies for right ventricular failure.
abstract: BACKGROUND
  Although right and left ventricular embryological origins, morphology and cardiodynamics differ, the notion of selectively targeted right ventricular therapies remains controversial.
  
  
  METHODS
  This review focuses on both the currently evolving pharmacologic agents targeting right ventricular failure (metabolic modulators, phosphodiesterase type V inhibitors) and future therapeutic approaches including epigenetic modulation by miRNAs, chromatin binding complexes, long non-coding RNAs, genomic editing, adoptive gene transfer and gene therapy, cell regeneration via cell transplantation and cell reprogramming and cardiac tissue engineering.
  
  
  CONCLUSIONS
  Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure. Instances of right ventricular failure requiring global reconstitution of right ventricular myocardium, attractive approaches include: i) myocardial patches seeded with cardiac fibroblasts reprogrammed into cardiomyocytes in vivo by small molecules, miRNAs or other epigenetic modifiers; and ii) administration of miRNAs, lncRNAs or small molecules by non-viral vector delivery systems targeted to fibroblasts (e.g., episomes) to stimulate in vivo reprogramming of fibroblasts into cardiomyocytes. For selected heritable genetic myocardial diseases, genomic editing affords exciting opportunities for allele-specific silencing by site-specific directed silencing, mutagenesis or gene excision. Genomic editing by adoptive gene transfer affords similarly exciting opportunities for restoration of myocardial gene expression.
authors.affiliation: Vanderbilt University Medical Center and School of Medicine, Vanderbilt Heat and Vascular Institute , Nashville, TN , USA +1 615 294 5437 ; +1 615 343 4841 ; Thomas.g.disalvo@vanderbilt.edu.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Di Salvo
mesh_terms: D065150:Cellular Reprogramming; D057890:Epigenomics; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000628:therapy*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism; D012038:Regeneration; D023822:Tissue Engineering
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding
keywords: epigenetic modulation; myocardial regeneration; right ventricular failure; targeted therapies