title: Differential expression of PDE5 in failing and nonfailing human myocardium.
abstract: BACKGROUND
  Recognizing that inhibitors of phosphodiesterase type 5 (PDE5) are increasingly employed in patients with pulmonary hypertension and right ventricular (RV) failure, we examined PDE5 expression in the human RV and its impact on myocardial contractility.
  
  
  RESULTS
  Tissue extracts from the RV of 20 patients were assayed for PDE5 expression using immunoblot and immunohistochemical staining. Tissues were selected from groups of nonfailing organ donors and transplant recipients with endstage ischemic cardiomyopathy or idiopathic dilated cardiomyopathy. Among dilated cardiomyopathy patients, subgroups with mild or severe RV dysfunction and prior left ventricular assist devices were analyzed separately. Our results showed that PDE5 abundance increased more than 4-fold in the RVs of the ischemic cardiomyopathy compared with the nonfailing group. In dilated cardiomyopathy, PDE5 upregulation was more moderate and varied with the severity of RV dysfunction. Immunohistochemical staining confirmed that cardiac myocytes contributed to the upregulation in the failing hearts. In functional studies, PDE5 inhibition produced little change in developed force in RV trabeculae from nonfailing hearts but produced a moderate increase in RV trabeculae from failing hearts.
  
  
  CONCLUSIONS
  Our results showed the etiology- and severity-dependent upregulation of myocyte PDE5 expression in the RV and the impact of this upregulation on myocardial contractility. These findings suggest that RV PDE5 expression could contribute to the pathogenesis of RV failure, and direct myocardial responses to PDE5 inhibition may modulate the indirect responses mediated by RV afterload reduction.
authors.affiliation: Cardiovascular Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Shan
authors.forename: Michael P
authors.initials: MP
authors.lastname: Quaile
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Monk
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D009202:Cardiomyopathies / Q000201:enzymology* / Q000601:surgery; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000601:surgery; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D005260:Female; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D012720:Severity of Illness Index; D014019:Tissue Donors; D014180:Transplantation
chemical_list: D015415:Biomarkers; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5