Ercu Maria, Klussmann Enno
Max Delbrück Center for Molecular Medicine Berlin (MDC), Berlin 13125, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Berlin 13347, Germany.
J Cardiovasc Dev Dis. 2018 Feb 20;5(1):14. doi: 10.3390/jcdd5010014.
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.
A激酶锚定蛋白（AKAPs）和环核苷酸磷酸二酯酶（PDEs）是环磷酸腺苷（cAMP）信号级联反应中的关键酶。它们通过控制环核苷酸依赖性信号传导的强度、持续时间和区域化来建立局部cAMP池。AKAP和PDE家族的各种成员在心血管系统中表达，并指导维持心脏和血管系统稳态功能的重要过程，例如内皮屏障功能和兴奋-收缩偶联。AKAP和PDE功能失调与心血管系统的病理生理状况有关，包括心力衰竭、高血压和动脉粥样硬化。包括常染色体显性遗传性短指高血压（HTNB）和I型长QT综合征（LQT1）在内的许多疾病，都是由编码这两类酶不同成员的基因突变引起的。本综述概述了与心脏和血管系统中cAMP区域化相关的AKAPs和PDEs，并讨论了它们的病理生理作用，同时强调了靶向这些蛋白及其蛋白-蛋白相互作用治疗心血管疾病的潜在益处。
