Endothelin-1 and Neuregulin-1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse

Patel, Rita; Kos, Lidia

doi:10.1002/dvdy.20284

Cited by 44 publications

(39 citation statements)

References 88 publications

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“…SAN cell proliferation continues until shortly before birth (36). A number of signaling pathways, including neuregulin/ErbB, endothelin, and Notch signaling pathways, have been implicated in various aspects of atrioventricular and ventricular conduction system development (37)(38)(39)(40)(41)(42); however, our understanding of signaling pathways regulating proliferation and differentiation of SAN cells and their progenitors is limited.…”

Section: Isl1 Is Expressed In Cardiac Pacemaker Cells Of the Sanmentioning

confidence: 99%

Transcription factor ISL1 is essential for pacemaker development and function

Liang¹,

Zhang²,

Cattaneo³

et al. 2015

J. Clin. Invest.

102

125

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(X. Liang).Statistics. Data are presented as mean ± SEM, and a 2-tailed t test was used for 2-group comparisons. Differences were considered statistically significant at a value of P < 0.05.Study approval. All the experiments involving mice were carried out in accordance with protocols approved by the Institutional Animal Care and Use Committee of USCD (A3033-01) and by the Animal Committee of Tongji University School of Medicine (TJmed-010-10).

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Section: Isl1 Is Expressed In Cardiac Pacemaker Cells Of the Sanmentioning

confidence: 99%

Transcription factor ISL1 is essential for pacemaker development and function

Liang¹,

Zhang²,

Cattaneo³

et al. 2015

J. Clin. Invest.

102

125

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“…ErbB3-null mice exhibit cardiac cushion abnormalities, leading to reflux of blood through defective valves. 18,19 Interestingly, apart from its role in ventricular trabeculation and cardiac cushion formation, NRG-1 also converts embryonic cardiomyocytes into cells of the conduction system 20,21 and promotes differentiation and survival of cardiomyocytes derived from embryonic stem cells 22 (Table 1).…”

Section: Role Of Nrg-1 In the Fetal Heartmentioning

confidence: 99%

Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease

2007

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Abstract-Since the discovery that neuregulin-1 (NRG-1)/ErbB signaling is indispensable in cardiac development, evidence has shown that this system also plays a crucial role in the adult heart. In patients, an inhibitory ErbB2 antibody, trastuzumab, used in the treatment of mammary carcinomas, increases the risk for the development of cardiotoxic cardiomyopathy. Postnatal disruption of NRG-1/ErbB signaling by gene targeting in mice leads to dilated cardiomyopathy. Initially, the search for the mechanisms behind these observations focused mainly on the effects of NRG-1 on cardiomyocyte growth and survival and revealed that NRG-1 has Akt-dependent antiapoptotic effects in cultured cardiomyocytes. In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. More recent studies have revealed that NRG-1 is involved in the regulation of cardiac sympathovagal balances by counterbalancing adrenergic stimulation of the adult myocardium and through an obligatory interaction with the muscarinic cholinergic system. NRG-1 is synthesized and released by the endocardial and cardiac microvascular endothelium, dynamically controlled by neurohormonal and biomechanical stimuli. The physiology of the cardiac NRG-1/ErbB system has implications for the treatment of both cancer and heart failure. Clinical studies in breast cancer with novel ErbB inhibitors are currently underway. Novel oncological indications for ErbB inhibition are emerging; cardiovascular side effects need to be carefully monitored. On the other hand, pharmacological activation of ErbB signaling is likely an unrecognized and beneficial effect of currently used drugs in heart failure and a promising therapeutic approach to prevent or reverse myocardial dysfunction. Key Words: endothelium Ⅲ receptors, ErbB-2 Ⅲ heart failure Ⅲ neuregulins N euregulin-1 (NRG-1) is a member of the epidermal growth factor (EGF) family known to activate proliferation, differentiation, and survival of many tissue types, including breast epithelial cells, glial cells, neurons, and myocytes. 1-4 Its biological effects are mediated by a set of tyrosine kinase receptors (ErbB2, ErbB3, and ErbB4) that dimerize on ligand binding, leading to phosphorylation and downstream signaling. 5 NRG-1 biology is complicated by the fact that multiple splice variants are produced from the NRG-1 gene (for review, see elsewhere 6 ). These NRG-1 isoforms can be divided into 3 types. Type I and II NRGs contain an immunoglobulin-like domain and are single-pass transmembrane proteins. Type III NRGs, containing a cysteine-rich domain, are 2-pass transmembrane proteins. Proteolytic cleavage of type I and II NRGs by members of the a-disintegrin and metalloprotease (ADAM) family such as tumor necrosis factor-␣ converting enzyme (ADAM17) and meltrin-␤ (ADAM19) 7,8 results in the release of a bioactive fragment. Cleavage of type III isoforms generates a transmembrane N-terminal fragment (Figure 1). 9 A common motif to all NRG isofo...

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“…These include endothelin-1 (Et1) and neuregulin 1 (Nrg1), both of which have been implicated as potential inducers of fast conduction (Gourdie et al, 1998;Hall et al, 2004;Milan et al, 2006;Patel and Kos, 2005;Rentschler et al, 2002;Sedmera et al, 2008;Takebayashi-Suzuki et al, 2000). Conversely, Bmp2 is highly expressed by the AVJ and is thought to be a negative regulator of Cx40 and Nav1.5 expression through its downstream targets Tbx2 and Tbx3 (Christoffels et al, 2004b;Hoogaars et al, 2004;Singh et al, 2012;Yamada et al, 2000;Boukens and Christoffels, 2012;van den Boogaard et al, 2012).…”

Section: Avj Myocytes Differentiate With Physiological Features Uniqumentioning

confidence: 99%

“…Several endocardial-derived factors have previously been reported to be inducers of fast conduction fate in myocardial cells at later stages of heart development (Gourdie et al, 1998;Hall et al, 2004;Patel and Kos, 2005;Rentschler et al, 2002;Sedmera et al, 2008;TakebayashiSuzuki et al, 2000). To date, however, it has yet to be examined whether the physical separation of endocardium from myocardium that occurs during cardiac jelly deposition plays a role in AVJ conduction patterning.…”

Section: Introductionmentioning

confidence: 99%

Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction

et al. 2014

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Efficient blood flow depends on two developmental processes that occur within the atrioventricular junction (AVJ) of the heart: conduction delay, which entrains sequential chamber contraction; and valve formation, which prevents retrograde fluid movement. Defects in either result in severe congenital heart disease; however, little is known about the interplay between these two crucial developmental processes. Here, we show that AVJ conduction delay is locally assigned by the morphogenetic events that initiate valve formation. Our data demonstrate that physical separation from endocardial-derived factors prevents AVJ myocardium from becoming fast conducting. Mechanistically, this physical separation is induced by myocardial-derived factors that support cardiac jelly deposition at the onset of valve formation. These data offer a novel paradigm for conduction patterning, whereby reciprocal myocardialendocardial interactions coordinate the processes of valve formation with establishment of conduction delay. This, in turn, synchronizes the electrophysiological and structural events necessary for the optimization of blood flow through the developing heart.

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Endothelin-1 and Neuregulin-1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse

Cited by 44 publications

References 88 publications

Transcription factor ISL1 is essential for pacemaker development and function

Transcription factor ISL1 is essential for pacemaker development and function

Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease

Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction

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