NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium

White, Mark P.; Theodoris, Christina V.; Liu, Lei; Collins, William J.; Blue, Kathleen W.; Lee, Woo Jung; Meng, Xianzhong; Robbins, Robert C.; Ivey, Kathryn N.; Srivastava, Deepak

doi:10.1016/j.yjmcc.2015.04.006

Cited by 47 publications

(51 citation statements)

References 43 publications

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“…Mutations in NOTCH1 have been linked with the presence of aortic valve calcification in human and mouse studies, although the disease was much milder in the latter . A recent study of NOTCH1 in human aortic VECs found that this factor positively regulated MGP . Shear stress was simulated by media flow conditions in vitro and was found to activate NOTCH1 expression .…”

Section: The Cardiovascular System Diseases and Insightsmentioning

confidence: 97%

Large animal models of cardiovascular disease

Tsang

Rashdan

Whitelaw

et al. 2016

Cell Biochemistry & Function

112

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The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone‐formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease. 2016 The Authors. Published by John Wiley & Sons Ltd.

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Section: The Cardiovascular System Diseases and Insightsmentioning

confidence: 97%

Large animal models of cardiovascular disease

Tsang

Rashdan

Whitelaw

et al. 2016

Cell Biochemistry & Function

112

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“…Notch1 is essential in endothelial cells for proper development of the vasculature (32) and in the endocardium for endocardial cushion formation and ventricular trabeculation (41,42). Roles for endothelial Notch1 have also been described in adult cardiovascular disease, including valve calcification (43,44 Figure 2). Several publications have demonstrated a less predominant role for Notch1 in SMC in the vasculature, including neointimal repair after injury (46)(47)(48).…”

Section: ;Fbn1mentioning

confidence: 99%

Notch1 haploinsufficiency causes ascending aortic aneurysms in mice

Koenig¹,

LaHaye²,

Feller³

et al. 2017

JCI Insight

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“…Mechanistically, MGP deletion results in increased Notch signaling via enhanced expression of the Notch ligand Jagged1 [75] and accordingly, deletion of a single Jagged1 or Jagged2 allele in MGP knockout animals suppresses arteriovenous malformations [77]. Although it is not yet clear how MGP controls Jagged1 expression, it appears that MGP expression is also controlled by Notch in shear-stressed aortic valve endothelium, [78] suggesting that Notch and MGP are coordinated by a feedback regulation.…”

Section: Indirect Ecm-notch Interactions That Control Notch Signalingmentioning

confidence: 99%

Notch: A multi-functional integrating system of microenvironmental signals

LaFoya

Munroe

Mia

et al. 2016

Developmental Biology

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The Notch signaling cascade is an evolutionarily ancient system that allows cells to interact with their microenvironmental neighbors through direct cell-cell interactions, thereby directing a variety of developmental processes. Recent research is discovering that Notch signaling is also responsive to a broad variety of stimuli beyond cell-cell interactions, including: ECM composition, crosstalk with other signaling systems, shear stress, hypoxia, and hyperglycemia. Given this emerging understanding of Notch responsiveness to microenvironmental conditions, it appears that the classical view of Notch as a mechanism enabling cell-cell interactions, is only a part of a broader function to integrate microenvironmental cues. In this review, we summarize and discuss published data supporting the idea that the full function of Notch signaling is to serve as an integrator of microenvironmental signals thus allowing cells to sense and respond to a multitude of conditions around them.

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NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium

Cited by 47 publications

References 43 publications

Large animal models of cardiovascular disease

Large animal models of cardiovascular disease

Notch1 haploinsufficiency causes ascending aortic aneurysms in mice

Notch: A multi-functional integrating system of microenvironmental signals

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