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December 1, 2014Journal of Cardiovascular Development and DiseaseOpen Access

NOTCH LOF blocked OSS-induced cell alignment in HUVECs, and in diseased AVICs, NOTCH LOF combined with OSS was associated with increased α-SMA expression.

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Why the study?

Does NOTCH loss of function combined with oscillatory shear stress alter cell alignment and matrix protein expression in human aortic valve interstitial cells?

Population

Healthy and diseased human aortic valve interstitial cells and human umbilical vein endothelial cells

Comparison

NOTCH loss of function combined with cyclic… vs Normal NOTCH function and/or baseline conditions…

Design

Preclinical

Authors

RGRichard GodbyMayo ClinicCMCharu MunjalCincinnati Children's Hospital Medical CenterAOAmy M. OpokaCincinnati Children's Hospital Medical Center

Discussion

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Overview

Hypothesis-generating for NOTCH-OSS interactions in calcific aortic valve disease; should not yet change practice.

Structured PICO

Does NOTCH loss of function combined with oscillatory shear stress alter cell alignment and matrix protein expression in human aortic valve interstitial cells?

P
Population
Healthy and diseased human aortic valve interstitial cells (AVICs) and human umbilical vein endothelial cells (HUVECs)
I
Intervention
NOTCH loss of function (LOF) combined with cyclic oscillatory shear stress (OSS) applied via an orbital shaker system
C
Comparator
Normal NOTCH function and/or baseline conditions without oscillatory shear stress
O
Outcome
Cell alignment and expression of elastin (ELN) and α-SMA (ACTA2)surrogate

The study demonstrates that complex NOTCH signaling interacts with biomechanical forces to regulate matrix homeostasis in healthy aortic valves and contributes to disorganization in calcific aortic valve disease.

Cite This Study

Godby et al. (2014) studied this question.

synapsesocial.com/papers/6a8a5feff8670bac6e3372c2https://doi.org/10.3390/jcdd1030237
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Also Consider

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  1. 1Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction2015 · 56 citations
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  5. 5Notch1 Promotes the Pro-Osteogenic Response of Human Aortic Valve Interstitial Cells via Modulation of ERK1/2 and Nuclear Factor-κB Activation2013 · 78 citations