Cinnamaldehyde alleviates pulmonary hypertension by affecting vascular remodeling through the TLR4/NF-kB/HIF-1a pathway

Objective: To investigate the mechanism by which cinnamaldehyde (CA) alleviates pulmonary arterial hypertension (PAH) through the TLR4/NF-kB/HIF-1a pathway.

Methods: PAH was induced in rats via SU5416 injection and hypoxia. Hemodynamics (RVMP, RVSP, mPAP) were measured. Histological changes were assessed by HE staining, and protein expressions of α-SMA, Col I, TLR4, p-p65, p65, and HIF-1a were detected by western blot. In vitro, hypoxia-induced HPAECs were treated with CA and TLR4 Activator RS09TFA. Cell function was assessed by CCK-8, colony formation, and scratch assays, with VE-Cadherin and α-SMA expression analyzed by western blot.

Results: PAH rats showed increased RVMP, RVSP, mPAP, and pulmonary artery thickening. CA significantly alleviated lung damage and reduced α-SMA and Col I expression. TLR4/NF-kB/HIF-1a activation with RS09TFA inhibited CA's effects. In vitro, CA mitigated hypoxia-induced HPAEC dysfunction, restoring VE-Cadherin and α-SMA expression, while RS09TFA blocked these effects.

Conclusion: CA alleviates PAH by inhibiting the TLR4/NF-kB/HIF-1a pathway and suppressing vascular remodeling, suggesting its potential as a therapeutic agent for PAH.

Cinnamaldehyde; TLR4; endothelial dysfunction; pulmonary arterial hypertension; vascular remodeling.