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.