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May 3, 2013Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

Inhibition or silencing of Notch1 suppressed the pro-osteogenic response (BMP-2 and ALP expression) and reduced ERK1/2 and NF-κB phosphorylation induced by LPS in diseased AVICs.

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Population

Human aortic valve interstitial cells (AVICs) isolated from diseased and normal human valves

Comparison

Inhibition or silencing of Notch1, or… vs Control AVICs without Notch1 modulation

Design

Preclinical

Authors

QZQingchun ZengRSRui SongLALihua Ao

Discussion

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Overview

Notch1 inhibition may represent a target in calcific aortic valve disease; hypothesis-generating from Level 5 data, requires in vivo and clinical validation.

Structured PICO

P
Population
Human aortic valve interstitial cells (AVICs) isolated from diseased and normal human valves
I
Intervention
Inhibition or silencing of Notch1, or stimulation with Notch1 ligand Jagged1, alongside lipopolysaccharide (LPS) stimulation
C
Comparator
Control AVICs without Notch1 modulation
O
Outcome
Expression of bone morphogenetic protein-2 and alkaline phosphatase, and phosphorylation of ERK1/2 and nuclear factor-κBsurrogate

Notch1 mediates the pro-osteogenic response to TLR4 stimulation in human aortic valve interstitial cells via ERK1/2 and NF-κB pathways, highlighting a potential therapeutic target for calcific aortic valve disease.

Cite This Study

Zeng et al. (2013) studied this question.

synapsesocial.com/papers/6a70e7eae5469ee92be193echttps://doi.org/10.1161/atvbaha.112.300912
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cross-Talk Between the Toll-Like Receptor 4 and Notch1 Pathways Augments the Inflammatory Response in the Interstitial Cells of Stenotic Human Aortic Valves2012 · 79 citations
  2. 2Augmented Osteogenic Responses in Human Aortic Valve Cells Exposed to oxLDL and TLR4 Agonist: A Mechanistic Role of Notch1 and NF-κB Interaction2014 · 34 citations
  3. 3Inhibitory Role of Notch1 in Calcific Aortic Valve Disease2011 · 113 citations
  4. 4Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction2015 · 56 citations
  5. 5Endothelial Notch signaling as a target for aortic valve calcification2025