Endocardial Notch Signaling in Cardiac Development and Disease

Luxán, Guillermo; D’Amato, Gaetano; MacGrogan, Donal; Pompa, José Luis de la

doi:10.1161/circresaha.115.305350

Cited by 209 publications

(156 citation statements)

References 153 publications

(179 reference statements)

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“…The discovery that humans with heterozygous mutations in NOTCH1 displayed aortic valve disease was not surprising since Notch signaling plays a critical role in several cardiovascular diseases [24]. Binding of the Notch signaling pathway ligands (Jagged and Delta-like) to the Notch receptors (1–4) initiates a sequence of cleavages, releasing the Notch intracellular domain (NICD) for nuclear translocation and initiation of target gene expression.…”

Section: Molecular Pathways For Aortic Valve Developmentmentioning

confidence: 99%

“…Notch1 is the predominate receptor that functions in endothelial cells during cardiovascular development, where it is required for initiation of EMT, and persists after EMT throughout valve remodeling and into adulthood. Disruption of several Notch pathway members results in dysregulated EMT, leading to embryonic lethality and/or abnormal valve development [24]. …”

Section: Molecular Pathways For Aortic Valve Developmentmentioning

confidence: 99%

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Genetic basis of aortic valvular disease

Koenig

Lincoln

Garg

2017

Current Opinion in Cardiology

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Purpose of Review Aortic valve disease is relatively common and encompasses both congenital and acquired forms. Bicuspid aortic valve (BAV) is the most common type of cardiac malformation and predisposes to the development of calcific aortic valve disease (CAVD). Since the description of the link between NOTCH1 and BAV and CAVD approximately a decade ago, there have been significant advances in the genetic and molecular understanding of these diseases. Recent findings Recent work has defined the congenital cardiac phenotypes linked to mutations in NOTCH1 and in addition, novel etiologic genes for BAV have been discovered using new genetic technologies in humans. Furthermore, several mouse models of BAV have been described defining the role of endothelial Notch1 in aortic valve morphogenesis while others have implicated new genes. These murine models along with other cell-based studies have led to molecular insights in the pathogenesis of CAVD. Summary These findings provide important insights into the molecular and genetic basis of aortic valve malformations, including BAV, specifically highlighting the etiologic role of endothelial cells. In addition, numerous investigations in the mechanisms of CAVD demonstrate the importance of developmental origins and signaling pathways as well as communication between valve endothelial cells and the underlying interstitial cells in valve disease onset and progression.

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Section: Molecular Pathways For Aortic Valve Developmentmentioning

confidence: 99%

Section: Molecular Pathways For Aortic Valve Developmentmentioning

confidence: 99%

Genetic basis of aortic valvular disease

Koenig

Lincoln

Garg

2017

Current Opinion in Cardiology

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“…[12][13][14] In the heart, Notch is essential during development, [15,16] and it is inactivated in cardiomyocytes after birth. [14] However, its reactivation after myocardial damage indicates that Notch plays a key role in cardiac repair.…”

Section: Introductionmentioning

confidence: 99%

Spheroid three-dimensional culture enhances Notch signaling in cardiac progenitor cells

et al. 2017

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Cardiac progenitor cells (CPCs) are a promising candidate for cardiac regeneration, and the interaction between CPCs and their microenvironment can influence their regenerative response. Notch signaling plays a key role in cell fate decisions in the developing and adult heart. Here, we investigated the effect of three-dimensional (3D) spheroid culture, as a model of the 3D microenvironment, on Notch in fetal and adult human CPCs, under room air (20%) and physiological (5%) oxygen tension. Notch signaling is enhanced in 3D spheroids; spheroid culture under 5% O 2 further increases Notch signaling enhancement, and might ultimately improve the regenerative potential of CPCs.

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“…As it is known that although there are tons of causes contributing to mental retardation, genetic factors are of particular concern. Notch signaling is a conserved developmental pathway that has an essential role in development of multiple organ systems [Luxán et al, 2016;Siebel and Lendahl, 2017]. Recent research shows that the Notch signaling pathway is critical for proliferation, migration, and differentiation of the neurons during embryonic development [Byun et al, 2017], with DLL1 playing an important part in these physiological processes [Imai et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Liu

Wang

Wei

et al. 2018

Cytogenet Genome Res

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Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

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Endocardial Notch Signaling in Cardiac Development and Disease

Cited by 209 publications

References 153 publications

Genetic basis of aortic valvular disease

Genetic basis of aortic valvular disease

Spheroid three-dimensional culture enhances Notch signaling in cardiac progenitor cells

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

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