期刊
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
卷 5, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/jcdd5010014
关键词
cAMP; compartmentalization; A-kinase anchoring proteins (AKAP); cyclic nucleotide phosphodiesterases (PDE); PDE inhibitors
资金
- Else Kroner-Fresenius-Stiftung [2013_A145]
- German-Israeli Foundation [G.I.F.I-1210-286.13/2012]
- German Centre for Cardiovascular Research [DZHK 81X210012, B18-005 SE]
- Deutsche Forschungsgemeinschaft [DFG KL1415/7-1]
- Bundesministerium fur Bildung und Forschung (BMBF) [16GW0179K]
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.
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