INSERM, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Cells. 2021 Apr 16;10(4):922. doi: 10.3390/cells10040922.
Under physiological conditions, cAMP signaling plays a key role in the regulation of cardiac function. Activation of this intracellular signaling pathway mirrors cardiomyocyte adaptation to various extracellular stimuli. Extracellular ligand binding to seven-transmembrane receptors (also known as GPCRs) with G proteins and adenylyl cyclases (ACs) modulate the intracellular cAMP content. Subsequently, this second messenger triggers activation of specific intracellular downstream effectors that ensure a proper cellular response. Therefore, it is essential for the cell to keep the cAMP signaling highly regulated in space and time. The temporal regulation depends on the activity of ACs and phosphodiesterases. By scaffolding key components of the cAMP signaling machinery, A-kinase anchoring proteins (AKAPs) coordinate both the spatial and temporal regulation. Myocardial infarction is one of the major causes of death in industrialized countries and is characterized by a prolonged cardiac ischemia. This leads to irreversible cardiomyocyte death and impairs cardiac function. Regardless of its causes, a chronic activation of cardiac cAMP signaling is established to compensate this loss. While this adaptation is primarily beneficial for contractile function, it turns out, in the long run, to be deleterious. This review compiles current knowledge about cardiac cAMP compartmentalization under physiological conditions and post-myocardial infarction when it appears to be profoundly impaired.
在生理条件下，cAMP 信号在心脏功能调节中发挥着关键作用。该细胞内信号通路的激活反映了心肌细胞对各种细胞外刺激的适应。细胞外配体与七跨膜受体（也称为 G 蛋白偶联受体（GPCRs））结合，通过 G 蛋白和腺苷酸环化酶（ACs）调节细胞内 cAMP 含量。随后，这种第二信使触发特定细胞内下游效应物的激活，以确保适当的细胞反应。因此，细胞必须高度调控 cAMP 信号在时空上的传递。时间调节取决于 AC 和磷酸二酯酶的活性。通过支架细胞 cAMP 信号机制的关键组成部分，蛋白激酶 A 锚定蛋白（AKAPs）协调时空调节。心肌梗死是工业化国家主要死亡原因之一，其特征是长期的心肌缺血。这会导致不可逆的心肌细胞死亡和心脏功能受损。无论其原因如何，心脏 cAMP 信号的慢性激活是为了弥补这种损失。虽然这种适应主要有利于收缩功能，但从长远来看，它是有害的。本综述汇集了目前关于生理条件下和心肌梗死后心脏 cAMP 区室化的知识，后者似乎受到严重损害。
