Document Detail


Differential expression of PDE5 in failing and nonfailing human myocardium.
MedLine Citation:
PMID:  22135403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODS AND 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:
Xiaoyin Shan; Michael P Quaile; Jeffery K Monk; Benjamin French; Thomas P Cappola; Kenneth B Margulies
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-01
Journal Detail:
Title:  Circulation. Heart failure     Volume:  5     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-18     Completed Date:  2012-04-13     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-86     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Biological Markers / metabolism
Cardiomyopathies / enzymology*,  surgery
Cardiomyopathy, Dilated / enzymology*,  surgery
Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism*
Female
Heart Transplantation
Heart Ventricles / enzymology*,  physiopathology
Humans
Male
Middle Aged
Myocardial Contraction / physiology
Myocardium / enzymology*
Myocytes, Cardiac / enzymology
Severity of Illness Index
Tissue Donors
Transplantation
Grant Support
ID/Acronym/Agency:
AG17022/AG/NIA NIH HHS; HL089847/HL/NHLBI NIH HHS; R01 AG017022-11/AG/NIA NIH HHS; R01 HL088577/HL/NHLBI NIH HHS; R01 HL089847-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5
Comments/Corrections

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