Baicalein attenuates monocrotaline-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition.

Abstract

AIMS:

Endothelial-to-mesenchymal transition (EndoMT) was shown to lead to endothelial cell (EC) dysfunction in pulmonary arterial hypertension (PAH). Baicalein was reported to inhibit epithelial-to-mesenchymal transition (EMT), a biological process that has many regulatory pathways in common with EndoMT. Whether it can attenuate PAH by inhibiting EndoMT remains obscure.

MAIN METHODS:

PAH was induced by a single subcutaneous injection of MCT (60 mg/kg) in male Sprague Dawley rats. Two weeks after MCT administration, the rats in the treatment groups received baicalein orally (50 or 100 mg/kg/day) for an additional 2 weeks. Hemodynamic changes and right ventricular hypertrophy (RVH) were evaluated on day 28. Cardiopulmonary interstitial fibrosis was detected using Masson's trichrome, Picrosirius-red, and immunohistochemical staining. The reactivity of pulmonary arteries (PAs) was examined ex vivo. The protein expresson of EndoMT molecules, bone morphogenetic protein receptor 2 (BMPR2), and nuclear factor-κB (NF-κB) was examined to explore the mechanism of protective action of baicalein.

KEY FINDINGS:

Baicalein (50 and 100 mg/kg) significantly alleviated MCT-induced PAH and cardiopulmonary interstitial fibrosis. Furthermore, baicalein treatment enhanced PA responsiveness to acetylcholine (ACh) in PAH rats. The upregulation of EndoMT molecules (N-cadherin, vimentin, Snail, and Slug) strongly suggest that EndoMT participates in MCT-induced PAH, which was reversed by baicalein (50 and 100 mg/kg) treatment. Moreover, baicalein partially reversed MCT-induced reductions in BMPR2 and NF-κB activation in the PAs.

SIGNIFICANCE:

Baicalein attenuated MCT-induced PAH in rats by inhibiting EndoMT partially via the NF-κB-BMPR2 pathway. Thus, baicalein might be considered as a promising treatment option for PAH.

• Authors: Ruizan Shi, Diying Zhu, Zehui Wei, Naijie Fu, Chang Wang, Linhong Liu, Huifeng Zhang, Yueqin Liang, Jianfeng Xing, Xuening Wang, Yan Wang
• Journal: Life sciences (Life Sci) Vol. 207 Pg. 442-450 (Aug 15 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29969608 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Flavanones
• NF-kappa B
• baicalein
• Monocrotaline
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Endothelium (drug effects)
• Enzyme Inhibitors (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Flavanones (pharmacology)
• Hemodynamics
• Hypertension, Pulmonary (chemically induced, drug therapy)
• Male
• Mesoderm (drug effects)
• Monocrotaline
• NF-kappa B (metabolism)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation