Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to
Peter Pokreisz1, Sara Vandenwijngaert, Virginie Bito
1Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium.
Circulation
|January 14, 2009
Summary
Increased phosphodiesterase-5 (PDE5) expression worsens left ventricular remodeling after heart attack. This finding suggests PDE5 is a therapeutic target for heart failure patients with cardiomyopathy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Pathophysiology
Background:
- Ventricular phosphodiesterase-5 (PDE5) expression is elevated in right ventricular hypertrophy.
- The role of PDE5 in left ventricular (LV) failure is not fully understood.
- This study investigates PDE5's role in LV remodeling and heart failure.
Purpose of the Study:
- To measure LV PDE5 expression in patients with advanced systolic heart failure.
- To characterize LV remodeling post-myocardial infarction in mice overexpressing PDE5.
- To explore PDE5 as a potential therapeutic target in heart failure.
Main Methods:
- Immunoblot and immunohistochemistry to assess PDE5 expression in human hearts.
- Generation of transgenic mice with cardiomyocyte-specific PDE5 overexpression (PDE5-TG).
- Assessment of cardiac function, remodeling, and cardiomyocyte properties in PDE5-TG and wild-type mice post-myocardial infarction.
Main Results:
- PDE5 expression was significantly higher in LVs of patients with dilated and ischemic cardiomyopathy compared to controls.
- PDE5-TG mice showed increased PDE5 expression in cardiomyocytes, localized to Z-bands.
- Post-myocardial infarction, PDE5-TG mice exhibited exacerbated LV dilation, systolic and diastolic dysfunction, and reduced cardiomyocyte contractility compared to wild-type littermates.
Conclusions:
- Increased PDE5 expression promotes adverse LV remodeling following myocardial infarction in mice.
- Elevated myocardial PDE5 in patients with advanced cardiomyopathy may contribute to heart failure development.
- Targeting myocardial PDE5 represents a potential therapeutic strategy for heart failure.
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