SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1.

ABSTRACT:

Background

Endothelial-mesenchymal transition (EndMT) plays a crucial role in promoting myocardial fibrosis and exacerbating cardiac dysfunction. Dapagliflozin (DAPA) is a sodium-glucose-linked transporter 2 (SGLT-2) inhibitor that has been shown to improve cardiac function in non-diabetic patients with heart failure (HF). However, the precise mechanisms by which DAPA exerts its beneficial effects are yet to be fully elucidated.

Methods

Isoproterenol (ISO) was used to generate a HF model in mice. For in vitro experiments, we used TGF-β1-stimulated human umbilical vein endothelial cells (HUVECs) and mouse aortic endothelial cells (MAECs).

Results

Both our in vivo and in vitro results showed that EndMT occurred with decreased SIRT1 (NAD⁺-dependent deacetylase

SUBMITTER: Wang W 

PROVIDER: S-EPMC10685714 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature