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September 10, 2012Circulation

Diseased cells exhibited augmented Jagged1 release and Notch1 activation after TLR4 stimulation, and inhibition of Notch1 abrogated the difference in NF-κB activation between diseased and normal cells.

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Population

Human aortic valve interstitial cells (AVIC) isolated from normal and stenotic leaflets

Comparison

TLR4 stimulation with lipopolysaccharide, with… vs Normal vs. stenotic AVICs, and untreated controls

Design

Preclinical

Authors

QZQingchun ZengCJChunhua JinLALihua Ao

Discussion

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Overview

May support Notch inhibition as a target in calcific aortic stenosis; hypothesis-generating in animal models and requires human validation.

Structured PICO

P
Population
Human aortic valve interstitial cells (AVIC) isolated from normal and stenotic leaflets
I
Intervention
TLR4 stimulation with lipopolysaccharide (LPS), with or without Notch1 modulation (inhibitor, siRNA, specific ligand Jagged1)
C
Comparator
Normal vs. stenotic AVICs, and untreated controls
O
Outcome
NF-κB activation and production of inflammatory markers (interleukin-8, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1)surrogate

Excessive cross-talk between the TLR4 and Notch1 pathways augments the inflammatory response in interstitial cells of stenotic human aortic valves, providing a potential mechanistic target for calcific aortic stenosis.

Cite This Study

Zeng et al. (2012) studied this question.

synapsesocial.com/papers/6a70e7eae5469ee92be193edhttps://doi.org/10.1161/circulationaha.111.083675
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Also Consider

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

  1. 1Notch1 Promotes the Pro-Osteogenic Response of Human Aortic Valve Interstitial Cells via Modulation of ERK1/2 and Nuclear Factor-κB Activation2013 · 78 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. 3Macrophages Promote Aortic Valve Cell Calcification and Alter STAT3 Splicing2020 · 44 citations
  4. 4Macrophages Promote Aortic Valve Cell Calcification Through STAT3 Splicing2020 · 1 citations
  5. 5Inhibitory Role of Notch1 in Calcific Aortic Valve Disease2011 · 113 citations