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

IntroductionCyclic 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 coveredOnly 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 opinionCurrently, 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.

Automated summary

This article discusses the research status of cAMP levels in heart diseases, and finds that there is currently no consensus on the levels of cAMP in human failing hearts. However, many studies indicate that cAMP levels are deficient in human failing hearts, suggesting that strategies to increase rather than decrease these levels should be pursued.