Clinical pharmacology of cardiac cyclic AMP in human heart failure: too much or too little?

Document Type

Article

Publication Date

7-12-2023

Publication Title

Expert Review of Clinical Pharmacology

Keywords

Adenylyl cyclase, cardiac function, cyclic AMP, G protein-coupled receptor, heart failure, human heart, protein kinase a, signal transduction

ISSN

1751-2441

Volume

16

Issue/No.

7

First Page

623

Last Page

630

Abstract

INTRODUCTION: Cyclic 3', 5'-adenosine monophosphate (cAMP) is a major signaling hub in cardiac physiology. Although cAMP signaling has been extensively studied in cardiac cells and animal models of heart failure (HF), not much is known about its actual amount present inside human failing or non-failing cardiomyocytes. Since many drugs used in HF work via cAMP, it is crucial to determine the status of its intracellular levels in failing vs. normal human hearts.

AREAS COVERED: Only studies performed on explanted/excised cardiac tissues from patients were examined. Studies that contained no data from human hearts or no data on cAMP levels per se were excluded from this perspective's analysis.

EXPERT OPINION: Currently, there is no consensus on the status of cAMP levels in human failing vs. non-failing hearts. Several studies on animal models may suggest maladaptive (e.g. pro-apoptotic) effects of cAMP on HF, advocating for cAMP lowering for therapy, but human studies almost universally indicate that myocardial cAMP levels are deficient in human failing hearts. It is the expert opinion of this perspective that intracellular cAMP levels are too low in human failing hearts, contributing to the disease. Strategies to increase (restore), not decrease, these levels should be pursued in human HF.

Comments

Funding

The author is supported by a grant from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (R01 #HL155718-01).

DOI

10.1080/17512433.2023.2233891

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Peer Reviewed

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