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Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

by Maria Ercu 1 and Enno Klussmann 1,2,*
1
Max Delbrück Center for Molecular Medicine Berlin (MDC), Berlin 13125, Germany
2
DZHK (German Centre for Cardiovascular Research), partner site Berlin 13347, Germany
*
Author to whom correspondence should be addressed.
J. Cardiovasc. Dev. Dis. 2018, 5(1), 14; https://doi.org/10.3390/jcdd5010014
Received: 31 January 2018 / Revised: 16 February 2018 / Accepted: 18 February 2018 / Published: 20 February 2018
(This article belongs to the Special Issue Cyclic Nucleotide Signaling and the Cardiovascular System)
A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases (PDEs) are essential enzymes in the cyclic adenosine 3’-5’ monophosphate (cAMP) signaling cascade. They establish local cAMP pools by controlling the intensity, duration and compartmentalization of cyclic nucleotide-dependent signaling. Various members of the AKAP and PDE families are expressed in the cardiovascular system and direct important processes maintaining homeostatic functioning of the heart and vasculature, e.g., the endothelial barrier function and excitation-contraction coupling. Dysregulation of AKAP and PDE function is associated with pathophysiological conditions in the cardiovascular system including heart failure, hypertension and atherosclerosis. A number of diseases, including autosomal dominant hypertension with brachydactyly (HTNB) and type I long-QT syndrome (LQT1), result from mutations in genes encoding for distinct members of the two classes of enzymes. This review provides an overview over the AKAPs and PDEs relevant for cAMP compartmentalization in the heart and vasculature and discusses their pathophysiological role as well as highlights the potential benefits of targeting these proteins and their protein-protein interactions for the treatment of cardiovascular diseases. View Full-Text
Keywords: cAMP; compartmentalization; A-kinase anchoring proteins (AKAP); cyclic nucleotide phosphodiesterases (PDE); PDE inhibitors cAMP; compartmentalization; A-kinase anchoring proteins (AKAP); cyclic nucleotide phosphodiesterases (PDE); PDE inhibitors
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Ercu, M.; Klussmann, E. Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System. J. Cardiovasc. Dev. Dis. 2018, 5, 14.

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