Dataset Information

Baicalin attenuates pulmonary vascular remodeling by inhibiting calpain-1 mediated endothelial-to-mesenchymal transition.

ABSTRACT:

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 p-AKT both in vitro and in vivo.

Conclusions

In conclusion, baicalin treatment attenuates PVR by inhibiting calpain-1 and PI3K/Akt-mediated EndMT.

SUBMITTER: Jiang HX

PROVIDER: S-EPMC10746466 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Baicalin attenuates pulmonary vascular remodeling by inhibiting calpain-1 mediated endothelial-to-mesenchymal transition.

Jiang He-Xi HX Wang Xiao-di XD Wang Hong-Xin HX Liu Tong T

Heliyon 20231130 12

<h4>Background</h4>Previous studies have demonstrated the beneficial effect of baicalin on pulmonary arterial hypertension (PAH), but the mechanism is unclear.<h4>Aim</h4>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).<h4>Methods</h4>PAH was induced by intraperitoneal injection of monocrotaline (MCT) in rats and hypoxia in calpain-1 gene knockout (Capn1<sup ...[more]

PMID: 38144352

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Project description:ObjectiveInterleukin-8 (IL-8) receptors IL8RA and IL8RB (IL8RA/B) on neutrophil membranes bind to IL-8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and inflammation. This study tested the hypothesis that administration of rat pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the adhesion of ECs to the injured lung and inhibit monocrotaline-induced pulmonary inflammation, arterial thickening and hypertension, and right ventricular hypertrophy.Approach and resultsThe treatment groups included 10-week-old ovariectomized Sprague-Dawley rats that received subcutaneous injection of PBS (vehicle), a single injection of monocrotaline (monocrotaline alone, 60 mg/kg, SC), monocrotaline followed by intravenous transfusion of ECs transduced with the empty adenoviral vector (null-EC), and monocrotaline followed by intravenous transfusion of ECs overexpressing IL8RA/B (1.5 × 10(6) cells/rat). Two days or 4 weeks after monocrotaline treatment, endothelial nitric oxide synthase, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant-2β (IL-8 equivalent in rat), and monocyte chemoattractant protein-1 expression, neutrophil and macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology were measured by histological and immunohistochemical techniques. Proinflammatory cytokine/chemokine protein levels were measured by Multiplex rat-specific magnetic bead-based sandwich immunoassay in total lung homogenates. Transfusion of ECs overexpressing IL8RA/B significantly reduced monocrotaline-induced neutrophil infiltration and proinflammatory mediator (IL-8, monocyte chemoattractant protein-1, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary arterial pressure, and pulmonary arterial and right ventricular hypertrophy and remodeling.ConclusionsThese provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature.

Dataset Information

Baicalin attenuates pulmonary vascular remodeling by inhibiting calpain-1 mediated endothelial-to-mesenchymal transition.

Background

Aim

Methods

Results

Conclusions

Publications

Baicalin attenuates pulmonary vascular remodeling by inhibiting calpain-1 mediated endothelial-to-mesenchymal transition.

Similar Datasets

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