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May 28, 2015Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction

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Population

Murine immortalized Notch1(+/-) aortic valve interstitial cells (AVICs) and wild-type AVICs

Comparison

Notch1 heterozygosity (Notch1 mutation) and… vs Wild-type AVICs

Design

Preclinical

Authors

JCJoseph ChenLRLarisa RyzhovaMSMary Kathryn Sewell-Loftin

Discussion

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Overview

In vitro Notch1 data support osteogenic CAVD mechanism; leaves open clinical translation and therapeutic targeting.

Structured PICO

P
Population
Murine immortalized Notch1(+/-) aortic valve interstitial cells (AVICs) and wild-type AVICs
I
Intervention
Notch1 heterozygosity (Notch1(+/-) mutation) and exposure to a dynamic mechanical environment (10% cyclic strain)
C
Comparator
Wild-type AVICs
O
Outcome
Cellular phenotype, molecular signaling (Akt phosphorylation, cadherin-11, Runx2, smooth muscle α-actin), and calcific nodule formationsurrogate

Notch1 heterozygosity promotes calcific aortic valve disease via Akt-mediated cadherin-11 expression and myofibroblast activation, resulting in dystrophic calcification.

Cite This Study

Chen et al. (2015) studied this question.

synapsesocial.com/papers/6a723909f44fa9f079dfc71bhttps://doi.org/10.1161/atvbaha.114.305095
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Also Consider

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

  1. 1Inhibitory Role of Notch1 in Calcific Aortic Valve Disease2011 · 113 citations
  2. 2Endothelial Notch signaling as a target for aortic valve calcification2025
  3. 3Notch1 Promotes the Pro-Osteogenic Response of Human Aortic Valve Interstitial Cells via Modulation of ERK1/2 and Nuclear Factor-κB Activation2013 · 78 citations
  4. 4Diet-Induced Aortic Valve Disease in Mice Haploinsufficient for the Notch Pathway Effector RBPJK/CSL2011 · 97 citations
  5. 5Cross Talk between NOTCH Signaling and Biomechanics in Human Aortic Valve Disease Pathogenesis2014 · 10 citations