The finding that PDE2 has a key role in the control of catecholamine-mediated signaling and on its functional effects may represent the starting point for further research exploring the possibility to use PDE2 as a target for therapy.

The cAMP transduction pathway is a key signaling system regulating the frequency and the strength of heart contraction. Several receptors expressed in cardiac myocytes mediate their downstream effects via the generatio of cAMP. It is well established that alteration of cAMP signaling associates with pathological conditions of the heart such as cardiac hypertrophy and heart failure.

Phosphodiesterases (PDEs) are a family of more then 50 enzymes whose function is to degrade cAMP inside the cell. Consequently, PDEs are key players in the control of the intracellular homeostasis of cAMP.

Our work identifies PDE2, a specific member of the PDE superfamily, as a key element in the hormonal control of heart function. We demonstrate that PDE2 is engaged in the control of the intracellular concentration of cAMP selectively in response to the binding of norepinephrine to beta-adrenergic receptors, supporting a model whereby cAMP signaling is highly compartmentalized in heart cells and PDE2 controls a spatially restricted pool of this second messenger.

Our work suggests that selective inhibition of PDE2 may represent a more specific and effective approach to the pharmacological manipulation of cAMP concentration and therefore a potential new venue for the treatment of heart disease.

We have been involved for several years in the study of the spatio-temporal dynamics of cAMP signaling in cardiac myocytes and in defining the role of PDEs in shaping the intracellular gradients of this second messenger.

Cardiovascular disease remains the number one cause of mortality in the Western world, with heart failure representing the fastest growing subclass over the past decade, resulting in a total economic impact as high as 100 billion USD per year.