Phosphodiesterase expression in the normal and failing heart.

Abstract

The number of patients with heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) is increasing, and for HFpEF, no therapies have clinical benefit. It has been hypothesized that PKG attenuates pathological remodelling, and increasing cGMP would be beneficial for patients with HF. However, neither the RELAX nor NEAT-HFpEF trial showed benefit. But there is still enthusiasm for increasing cGMP in patients with HF, which highlight the need to determine the expression of PDEs in cardiac muscle. This study used immunoblotting to examine the expression of the PDEs that have been suggested to be targets for therapy of HF in both canines (normal and HFpEF) and humans (normal and HFrEF). Our results demonstrate PDE1C and PDE3A are expressed in cardiac muscle, but we could not detect the expression of PDE2A, PDE5A, PDE7A and PDE9A in cardiac tissue lysates from either normal or failing hearts. Thus, one should not expect a clinical benefit for a therapy targeting these PDEs in heart failure, which highlights the importance of rigorous demonstration of the target of therapy prior to undertaking a clinical trial.

• Authors: Edwin A Li, Wang Xi, Young Soo Han, Frank V Brozovich
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 662 Pg. 160-168 (02 15 2019) ISSN: 1096-0384 [Electronic] United States
• PMID: 30550727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Relaxin
• Phosphoric Diester Hydrolases
• Cyclic GMP

Topics

• Adult
• Animals
• Case-Control Studies
• Cyclic GMP (metabolism)
• Humans
• Male
• Middle Aged
• Myocardium (enzymology, metabolism)
• Phosphoric Diester Hydrolases (metabolism)
• Relaxin (metabolism)