Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction.

ABSTRACT:

Objective

Calcific aortic valve disease (CAVD) is a significant cardiovascular disorder, and controversy exists as to whether it is primarily a dystrophic or osteogenic process in vivo. In this study, we sought to clarify the mechanism of CAVD by assessing a genetic mutation, Notch1 heterozygosity, which leads to CAVD with 100% penetrance in humans.

Approach and results

Murine immortalized Notch1(+/-) aortic valve interstitial cells (AVICs) were isolated and expanded in vitro. Molecular signaling of wild-type and Notch1(+/-) AVICs were compared to identify changes in pathways that have been linked to CAVD-transforming growth factor-β1/bone morphogenetic protein, mitogen-activated protein kinase, and phosphoinositide 3-kinase/protein kinase B-and assessed for calcification po

SUBMITTER: Chen J 

PROVIDER: S-EPMC4600070 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature