Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome

Yin, Jiani C.; Platt, Mathew J.; Tian, Xixi; Wu, Xue; Backx, Peter H.; Simpson, Jeremy A.; Araki, Toshiyuki; Neel, Benjamin G.

doi:10.1038/ncomms15518

Cited by 21 publications

(13 citation statements)

References 72 publications

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“…A research showed that the cardiac function of Ufl1 (ubiquitin-fold modifier 1) knockout mice began to deteriorate at 2 months and significant cardiac chamber dilation with interstitial fibrosis appeared at 6 months [155]. Another research confirmed that the EC-specific Raf1 L613V expression mice had myocardial hypertrophy and myocardial fibrosis 4 days after birth [156].…”

Section: L-namementioning

confidence: 98%

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Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

Ding

Wang

Jia

et al. 2020

International Journal of Hypertension

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Myocardial fibrosis is characterized by excessive deposition of myocardial interstitial collagen, abnormal distribution, and excessive proliferation of fibroblasts. According to the researches in recent years, myocardial fibrosis, as the pathological basis of various cardiovascular diseases, has been proven to be a core determinant in ventricular remodeling. Pressure load is one of the causes of myocardial fibrosis. In experimental models of pressure-overload-induced myocardial fibrosis, significant increase in left ventricular parameters such as interventricular septal thickness and left ventricular posterior wall thickness and the decrease of ejection fraction are some of the manifestations of cardiac damage. These morphological and functional changes have a serious impact on the maintenance of physiological functions. Therefore, establishing a suitable myocardial fibrosis model is the basis of its pathogenesis research. This paper will discuss the methods of establishing myocardial fibrosis model and compare the advantages and disadvantages of the models in order to provide a strong basis for establishing a myocardial fibrosis model.

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Section: L-namementioning

confidence: 98%

“…e technique of targeting vector of genomic DNA fragment plays an important role in model construction [155,156].…”

Section: L-namementioning

confidence: 99%

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

Ding

Wang

Jia

et al. 2020

International Journal of Hypertension

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“…Raf-1 kinase activity was essential for cardiac hypertrophy, enhanced MEK-ERK activity was critical for causing RAF1-mutant phenotypes. However, recently, Yin et al showed that left ventricular hypertrophy was due to the interplay of cardiac cell types [41]. Using inducible Even though RAS transgenic mice exhibited cardiac hypertrophy associated with cardiomyopathy, MEK1 transgenic mice showed a stable concentric hypertrophy without any signal of decompensation up to 12 months of age [42].…”

Section: Targeting Upstream Kinasementioning

confidence: 99%

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

Yan

Zeng

et al. 2021

Cardiol J.

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Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2(ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPKKs, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

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“…Patients in which the disease is caused by kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy, which is well reproduced in knock-in mice harbouring the Raf1(L613V/+) mutation. Interestingly, the EC-specific expression of the mutant protein is sufficient to drive cardiac hypertrophy and the secretion of IL-6 by Raf1(L613V/+)-expressing ECs is essential in promoting CM hypertrophy, clearly pointing to this interleukin as a key mediator of the EC-CM crosstalk during cardiac remodelling (Yin et al 2017).…”

Section: Endothelial Cell-cardiomyocyte Crosstalk During Cardiac Remomentioning

confidence: 99%

Endothelial cell–cardiomyocyte crosstalk in heart development and disease

Colliva

Braga

Giacca

et al. 2019

The Journal of Physiology

127

103

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The crosstalk between endothelial cells and cardiomyocytes has emerged as a requisite for normal cardiac development, but also a key pathogenic player during the onset and progression of cardiac disease. Endothelial cells and cardiomyocytes are in close proximity and communicate through the secretion of paracrine signals, as well as through direct cell-to-cell contact. Here, we provide an overview of the endothelial cell-cardiomyocyte interactions controlling heart Serena Zacchigna and Mauro Giacca serve as Professors of Molecular Biology at the University of Trieste, Italy and Principle Investigators of the Cardiovascular Biology and Molecular Medicine laboratories of the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste, Italy, respectively. Mauro Giacca also serves as the Director-General of the ICGEB. Andrea Colliva and Luca Braga are post-docs in the same laboratories. The main research interests of Serena Zacchigna focus around the mechanisms leading to new blood vessel formation in ischaemic muscles and hearts, whereas MauroGiacca is a leader in the field of cardiac regeneration, having particular interest in understanding why mammalian cardiomyocytes permanently exit from the cell cycle at birth and how this can be overcome therapeutically. The two laboratories have been extensively collaborating over the last few years to explore the intercellular crosstalk between cardiomyocytes and cardiac endothelial cells.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. 2A. Colliva and others J Physiol 00.0 development and the main processes affecting the heart in normal and pathological conditions, including ischaemia, remodelling and metabolic dysfunction. We also discuss the possible role of these interactions in cardiac regeneration and encourage the further improvement of in vitro models able to reproduce the complex environment of the cardiac tissue, in order to better define the mechanisms by which endothelial cells and cardiomyocytes interact with a final aim of developing novel therapeutic opportunities.Abstract figure legend Cardiomyocytes (labelled in red by anti-α-actinin antibodies) and endothelial cells (labelled in green by anti-CD31 antibodies) crosstalk in multiple ways, including paracrine communication (dashed arrows) through either secreted molecules or vesicles (red circles), direct cell-cell contact (hinges) and autocrine signalling (curved arrows). This crosstalk plays an important role during embryonic development, normal post-natal life and several pathological conditions, thus representing a novel target for the treatment of cardiovascular disorders.

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Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome

Cited by 21 publications

References 72 publications

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

Endothelial cell–cardiomyocyte crosstalk in heart development and disease

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