title: Cardiac Adenylyl Cyclase and Phosphodiesterase Expression Profiles Vary by Age, Disease, and Chronic Phosphodiesterase Inhibitor Treatment.
abstract: BACKGROUND
  Pediatric heart failure (HF) patients have a suboptimal response to traditional HF medications, although phosphodiesterase-3 inhibition (PDE3i) has been used with greater success than in the adult HF population. We hypothesized that molecular alterations specific to children with HF and HF etiology may affect response to treatment.
  
  
  RESULTS
  Adenylyl cyclase (AC) and phosphodiesterase (PDE) isoforms were quantified by means of quantitative real-time polymerase chain reaction in explanted myocardium from adults with dilated cardiomyopathy (DCM), children with DCM, and children with single-ventricle congenital heart disease of right ventricular morphology (SRV). AC and PDE expression profiles were uniquely regulated in each subject group and demonstratde distinct changes in response to chronic PDE3i. There was unique up-regulation of AC5 in adult DCM with PDE3i (fold change 2.415; P = .043), AC2 in pediatric DCM (fold change 2.396; P = .0067), and PDE1C in pediatric SRV (fold change 1.836; P = .032). Remarkably, PDE5A expression was consistently increased across all age and disease groups.
  
  
  CONCLUSIONS
  Unique regulation of AC and PDE isoforms supports a differential molecular adaptation to HF in children compared with adults, and may help identify mechanisms specific to the pathogenesis of pediatric HF. Greater understanding of these differences will help optimize medical therapies based on age and disease process.
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Nakano
authors.affiliation: University of Colorado, Boulder, Colorado.
authors.forename: Juliana
authors.initials: J
authors.lastname: Sucharov
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Robert
authors.initials: R
authors.lastname: van Dusen
authors.affiliation: University of Colorado, Boulder, Colorado.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Cecil
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors.forename: Karin
authors.initials: K
authors.lastname: Nunley
authors.affiliation: University of Denver, Denver, Colorado.
authors.forename: Sean
authors.initials: S
authors.lastname: Wickers
authors.affiliation: Department of Pharmacology, University of Colorado, Aurora, Colorado.
authors.forename: Anis
authors.initials: A
authors.lastname: Karimpur-Fard
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado; Division of Cardiology, Department of Medicine, Denver Health and Hospital Authority, Denver, Colorado.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado.
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Miyamoto
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado. Electronic address: kika.sucharov@ucdenver.edu.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Sucharov
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000235:genetics*; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D010726:Phosphodiesterase Inhibitors; D012313:RNA; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases
keywords: Adenylyl cyclase; dilated cardiomyopathy; phosphodiesterase; single ventricle congenital heart disease