Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states

Malashicheva, Anna; Kostina, Aleksandra; Kostareva, Anna; Irtyuga, Olga; Гордеев, М. Л.; Uspensky, Vladimir

doi:10.1016/j.bbadis.2019.165631

Cited by 19 publications

(21 citation statements)

References 154 publications

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“…Signaling initiated by interactions between receptors and ligands expressed on neighboring VSMCs positively regulates the transcription of multiple transcripts including Acta2 and Pdgfbr (coding for PDGF-β receptor) [168][169][170]. Whereas Notch positively regulates VSMC specification during development, its role in the modulation of adult VSMC phenotypes is less clear, having been shown to promote both "contractile" and "synthetic" phenotypes, depending on the study [168,[171][172][173][174][175][176].…”

Section: Notch Signalingmentioning

confidence: 99%

“…However, Notch signaling antagonizes TGF-β signaling by reducing the expression of TGF-β receptor II via the induction of miR145 [180]; in turn, TGF-β antagonizes Notch signaling by decreasing the expression of Notch3 [181]. The expression of Notch ligands and receptors is dysregulated in TAA, and defective Notch signaling has been associated with TAA that develops in patients with malformations of the aortic valve [175,182,183].…”

Section: Notch Signalingmentioning

confidence: 99%

“…The perturbation of Notch signaling, a pathway that can both cooperate and antagonize TGF-β signaling during VSMC differentiation, increases susceptibility to aortic aneurysm [174][175][176]. Although the mechanisms remain unclear, loss-of-function mutations in NOTCH1 predispose to hereditary forms of aneurysms that associate with aortic valve defects [213][214][215][216]328].…”

Section: Notch1mentioning

confidence: 99%

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Insights on the Pathogenesis of Aneurysm through the Study of Hereditary Aortopathies

Creamer

Bramel

MacFarlane

2021

Genes

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Thoracic aortic aneurysms (TAA) are permanent and localized dilations of the aorta that predispose patients to a life-threatening risk of aortic dissection or rupture. The identification of pathogenic variants that cause hereditary forms of TAA has delineated fundamental molecular processes required to maintain aortic homeostasis. Vascular smooth muscle cells (VSMCs) elaborate and remodel the extracellular matrix (ECM) in response to mechanical and biochemical cues from their environment. Causal variants for hereditary forms of aneurysm compromise the function of gene products involved in the transmission or interpretation of these signals, initiating processes that eventually lead to degeneration and mechanical failure of the vessel. These include mutations that interfere with transduction of stimuli from the matrix to the actin–myosin cytoskeleton through integrins, and those that impair signaling pathways activated by transforming growth factor-β (TGF-β). In this review, we summarize the features of the healthy aortic wall, the major pathways involved in the modulation of VSMC phenotypes, and the basic molecular functions impaired by TAA-associated mutations. We also discuss how the heterogeneity and balance of adaptive and maladaptive responses to the initial genetic insult might contribute to disease.

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Section: Notch Signalingmentioning

confidence: 99%

Section: Notch Signalingmentioning

confidence: 99%

Section: Notch1mentioning

confidence: 99%

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Insights on the Pathogenesis of Aneurysm through the Study of Hereditary Aortopathies

Creamer

Bramel

MacFarlane

2021

Genes

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“…In the context of diabetes, these components are damaged, mainly by the activation of Notch signaling pathways ( Mathieson, 2011 ; Loeffler and Wolf, 2014 ). After the binding of Notch receptors to Notch ligands, such as Jagged-like and Delta-like, the C-terminal Notch intracellular domain (NICD) is cleaved from the cell membrane by γ-secretase and translocates into the nucleus, where the formation of recombination signal binding protein for immunoglobulin κJ region (Rbpj) and mastermind-like (MAML) proteins occurs in order to induce the expression of gene sets important for the development of the kidney ( Malashicheva et al., 2020 ). The Notch pathway is reactivated in renal tissue obtained from diabetic mice to regulate the expression of Notch ligands ( Niranjan et al., 2008 ).…”

Section: Rock2-induced Fibrosis Notch Activation and Inflammation Imentioning

confidence: 99%

“…Some of the contents of this review were generated based on the works of authors ( Fu et al., 2006 ; Matoba et al., 2010 ; Meyer-Schwesinger et al., 2012 ; Matoba et al., 2013 ; Shimizu et al., 2013 ; Loeffler and Wolf, 2014 ; Shimizu and Liao, 2016 ; Matoba et al., 2017 ; Malashicheva et al., 2020 ).…”

Section: Acknowledgmentsmentioning

confidence: 99%

The Physiology, Pathology, and Therapeutic Interventions for ROCK Isoforms in Diabetic Kidney Disease

et al. 2020

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Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine/threonine kinase that was originally identified as RhoA interacting protein. A diverse array of cellular functions, including migration, proliferation, and phenotypic modulation, are orchestrated by ROCK through a mechanism involving cytoskeletal rearrangement. Mammalian cells express two ROCK isoforms: ROCK1 (Rho-kinase b/ROKb) and ROCK2 (Rho-kinase a/ROKa). While both isoforms have structural similarities and are widely expressed across multiple tissues, investigations in gene knockout animals and cell-based studies have revealed distinct functions of ROCK1 and ROCK2. With respect to the kidney, inhibiting ROCK activity has proven effective for the preventing diabetic kidney disease (DKD) in both type 1 and type 2 diabetic rodent models. However, despite significant progress in the understanding of the renal ROCK biology over the past decade, the pathogenic roles of the ROCK isoforms is only beginning to be elucidated. Recent studies have demonstrated the involvement of renal ROCK1 in mitochondrial dynamics and cellular transdifferentiation, whereas ROCK2 activation leads to inflammation, fibrosis, and cell death in the diabetic kidney. This review provides a conceptual framework for dissecting the molecular underpinnings of ROCKdriven renal injury, focusing on the differences between ROCK1 and ROCK2.

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Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis

Debiec

Hamby

Jones

et al. 2020

Molec Gen & Gen Med

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Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states

Cited by 19 publications

References 154 publications

Insights on the Pathogenesis of Aneurysm through the Study of Hereditary Aortopathies

Insights on the Pathogenesis of Aneurysm through the Study of Hereditary Aortopathies

The Physiology, Pathology, and Therapeutic Interventions for ROCK Isoforms in Diabetic Kidney Disease

Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis

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