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 assess...

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Main Authors: Jinbo Zhang, Wenxin Zhang, Zhiyong Yang, Bingbing Fan, Chunhe Wang, Zhengkun Tian
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Clinical and Experimental Hypertension
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Online Access:https://www.tandfonline.com/doi/10.1080/10641963.2025.2486829
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Summary: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.
ISSN:1064-1963
1525-6006