Conditional deletion of RB1 in the Tie2 lineage leads to aortic valve regurgitation.

ABSTRACT:

Objective

Aortic valve disease is a complex process characterized by valve interstitial cell activation, disruption of the extracellular matrix culminating in valve mineralization occurring over many years. We explored the function of the retinoblastoma protein (pRb) in aortic valve disease, given its critical role in mesenchymal cell differentiation including bone development and mineralization.

Approach and results

We generated a mouse model of conditional pRb knockout (cKO) in the aortic valve regulated by Tie2-Cre-mediated excision of floxed RB1 alleles. Aged pRb cKO animals showed significantly more aortic valve regurgitation by echocardiography compared to pRb het control animals. The pRb cKO aortic valves had increased leaflet thickness without increased cellular prol

SUBMITTER: Freytsis M 

PROVIDER: S-EPMC5755794 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature