Inactivation of platelet-derived TGF-β1 attenuates aortic stenosis progression in a robust murine model.

ABSTRACT: Aortic stenosis (AS) is a degenerative heart condition characterized by fibrosis and narrowing of aortic valves (AV), resulting in high wall shear stress (WSS) across valves. AS is associated with high plasma levels of transforming growth factor-β1 (TGF-β1), which can be activated by WSS to induce organ fibrosis, but the cellular source of TGF-β1 is not clear. Here, we show that platelet-derived TGF-β1 plays an important role in AS progression. We first established an aggressive and robust murine model of AS, using the existing Ldlr ^-/- Apob^100/100 (LDLR) breed of mice, and accelerated AS progression by feeding them a high-fat diet (HFD). We then captured very high resolution images of AV movement and thickness and of blood flow velocity across th

SUBMITTER: Varshney R 

PROVIDER: S-EPMC6418501 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature