Baicalin attenuates pulmonary vascular remodeling by inhibiting calpain-1 mediated endothelial-to-mesenchymal transition.

Background: Previous studies have demonstrated the beneficial effect of baicalin on pulmonary arterial hypertension (PAH), but the mechanism is unclear.

Aim: The aim of the present study was to evaluate the effect of baicalin on pulmonary vascular remodeling (PVR) with a focus on calpain-1-mediated endothelial-to-mesenchymal transition (EndMT).

Methods: PAH was induced by intraperitoneal injection of monocrotaline (MCT) in rats and hypoxia in calpain-1 gene knockout (Capn1) and wild-type C57BL/6 mice. An in vitro PVR model was established in PASMCs and HPAECs.

Results: The data showed that baicalin treatment and calpain-1 inhibition alleviated MCT and hypoxia-induced increases in right ventricular systolic pressure (RVSP), prevented right ventricle hypertrophy and PVR, and attenuated cardiopulmonary fibrosis. Moreover, baicalin ameliorated PAH-induced EndMT, as evidenced by the suppressed expression of mesenchymal markers vimentin, and α-SMA and restored expression of endothelial markers CD31, and VE-cadherin. In vitro studies showed that baicalin treatment blocked TGF-β1-induced EndMT in HPAECs and abolished hypoxia-induced PASMC proliferation and migration. All the beneficial effects of baicalin on PVR in vitro and in vivo were accompanied by suppressed calpain-1 expression. Further study demonstrated that baicalin treatment and calpain-1 inhibition inhibited the enhanced expression of PI3K and -AKT both in vitro and in vivo.

Conclusions: In conclusion, baicalin treatment attenuates PVR by inhibiting calpain-1 and PI3K/Akt-mediated EndMT.