The role of A-kinase anchoring proteins in cardiac oxidative stress

Diviani, Dario; Osman, Halima; Delaunay, Marion; Kaiser, Simon

doi:10.1042/bst20190228

Cited by 11 publications

(16 citation statements)

References 70 publications

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“…In the heart, AKAPs have been shown to regulate multiple physiological responses including cardiac contraction, rhythm and energy production as well as pathological functions linked to the development of arrhythmias, cardiac hypertrophy, fibrosis, and heart failure [7,141,142]. Several studies indicate that altering AKAP expression and signaling in cardiomyocytes can significantly impact their ability to survive cardiac stress and consequently influence replacement fibrosis [33,140,[143][144][145]. Since these results have been extensively reviewed in recent years, in the next paragraphs we will mainly focus on recent findings highlighting the role of AKAP signaling in cardiac fibroblasts.…”

Section: A-kinase Anchoring Proteinsmentioning

confidence: 99%

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Delaunay

Osman

Kaiser

et al. 2019

Cells

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Myocardial stress and injury invariably promote remodeling of the cardiac tissue, which is associated with cardiomyocyte death and development of fibrosis. The fibrotic process is initially triggered by the differentiation of resident cardiac fibroblasts into myofibroblasts. These activated fibroblasts display increased proliferative capacity and secrete large amounts of extracellular matrix. Uncontrolled myofibroblast activation can thus promote heart stiffness, cardiac dysfunction, arrhythmias, and progression to heart failure. Despite the well-established role of myofibroblasts in mediating cardiac disease, our current knowledge on how signaling pathways promoting fibrosis are regulated and coordinated in this cell type is largely incomplete. In this respect, cyclic adenosine monophosphate (cAMP) signaling acts as a major modulator of fibrotic responses activated in fibroblasts of injured or stressed hearts. In particular, accumulating evidence now suggests that upstream cAMP modulators including G protein-coupled receptors, adenylyl cyclases (ACs), and phosphodiesterases (PDEs); downstream cAMP effectors such as protein kinase A (PKA) and the guanine nucleotide exchange factor Epac; and cAMP signaling organizers such as A-kinase anchoring proteins (AKAPs) modulate a variety of fundamental cellular processes involved in myocardial fibrosis including myofibroblast differentiation, proliferation, collagen secretion, and invasiveness. The current review will discuss recent advances highlighting the role of cAMP and AKAP-mediated signaling in regulating pathophysiological responses controlling cardiac fibrosis.

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Section: A-kinase Anchoring Proteinsmentioning

confidence: 99%

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Delaunay

Osman

Kaiser

et al. 2019

Cells

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“…The altered cAMP level observed at the OMM in mdx myocytes is relevant as it may contribute to development and progression of the CM. It is well established that cAMP, via PKA, plays an important role in integrating redox signalling and in attenuating the detrimental impact of oxidative stress in cardiac myocytes [ 53 ] and the defective cAMP signalling we observe at the OMM in neonatal dystrophic myocytes may be an important contributor to cell damage. In addition, the cAMP/PKA axis drives mitochondrial respiration in exercise [ 54 ].…”

Section: Discussionmentioning

confidence: 69%

Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from the mdx Model of Duchenne Muscular Dystrophy

Brescia

Chao

Koschinski

et al. 2020

IJMS

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Duchenne muscular dystrophy (DMD) is the most frequent and severe form of muscular dystrophy. The disease presents with progressive body-wide muscle deterioration and, with recent advances in respiratory care, cardiac involvement is an important cause of morbidity and mortality. DMD is caused by mutations in the dystrophin gene resulting in the absence of dystrophin and, consequently, disturbance of other proteins that form the dystrophin-associated protein complex (DAPC), including neuronal nitric oxide synthase (nNOS). The molecular mechanisms that link the absence of dystrophin with the alteration of cardiac function remain poorly understood but disruption of NO-cGMP signalling, mishandling of calcium and mitochondrial disturbances have been hypothesized to play a role. cGMP and cAMP are second messengers that are key in the regulation of cardiac myocyte function and disruption of cyclic nucleotide signalling leads to cardiomyopathy. cGMP and cAMP signals are compartmentalised and local regulation relies on the activity of phosphodiesterases (PDEs). Here, using genetically encoded FRET reporters targeted to distinct subcellular compartments of neonatal cardiac myocytes from the DMD mouse model mdx, we investigate whether lack of dystrophin disrupts local cyclic nucleotide signalling, thus potentially providing an early trigger for the development of cardiomyopathy. Our data show a significant alteration of both basal and stimulated cyclic nucleotide levels in all compartments investigated, as well as a complex reorganization of local PDE activities.

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“…In contrast, AKAP12 overexpression suppresses the Ang-II-induced TGF-β1 signaling activation and fibrosis, supporting the cardioprotective properties of AKAP12 ( Table 2 ; Figure 2 D). Of note, the cardioprotective function of AKAP12 in cardiac fibroblasts has been previously reviewed [ 172 ].…”

Section: A-kinase Anchoring Proteins (Akap)mentioning

confidence: 99%

Cardiac cAMP-PKA Signaling Compartmentalization in Myocardial Infarction

Colombe

Pidoux

2021

Cells

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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.

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The role of A-kinase anchoring proteins in cardiac oxidative stress

Cited by 11 publications

References 70 publications

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from the mdx Model of Duchenne Muscular Dystrophy

Cardiac cAMP-PKA Signaling Compartmentalization in Myocardial Infarction

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