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Cinnamaldehyde alleviates pulmonary hypertension by affecting vascular remodeling through the TLR4/NF-kB/HIF-1a
Jinbo Zhang1, Wenxin Zhang2, Zhiyong Yang3
1Department of Preventive Treatment, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong, China.
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.
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