Pirfenidone and nintedanib attenuates pulmonary artery endothelial and smooth muscle cells transformations induced by IL-11
Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery remodeling. Serum and parenchyma levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients and contributes to pulmonary arter...
| Authors: | , , , |
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| Format: | article |
| Publication Date: | 2024 |
| Country: | España |
| Institution: | Universidad Europea (UEM) |
| Repository: | ABACUS. Repositorio de Producción Científica |
| Language: | English |
| OAI Identifier: | oai:abacus.universidadeuropea.com:11268/12878 |
| Online Access: | http://hdl.handle.net/11268/12878 |
| Access Level: | Open access |
| Keyword: | Fibrosis pulmonar Tratamiento farmacológico combinado Interleucina-11 Aparato respiratorio Tratamiento médico Goal 3: Ensure healthy lives and promote well-being for all at all ages |
| Summary: | Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery remodeling. Serum and parenchyma levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients and contributes to pulmonary artery remodeling and PH. However, the effect of current approved therapies against IPF in pulmonary artery remodeling induced by IL-11 is unknown. The aim of this study is to analyze the effects of nintedanib and pirfenidone on pulmonary artery endothelial and smooth muscle cell remodeling induced by IL-11 in vitro. Our results show that nintedanib (NTD) and pirfenidone (PFD) ameliorates endothelial to mesenchymal transition (EnMT), pulmonary artery smooth muscle cell to myofibroblast-like transformation and pulmonary remodeling in precision lung cut slices. This study provided also evidence of the inhibitory effect of PFD and NTD on IL-11-induced endothelial and muscle cells proliferation and senescence. The inhibitory effect of these drugs on monocyte arrest and angiogenesis was also studied. Finally, we observed that IL-11 induced canonical signal transducer and activator of transcription 3 (STAT3) and non-canonical mitogen-activated protein kinase 1/2 (ERK1/2) phosphorylation, but, PFD and NTD only inhibited ERK1/2 phosphorylation. Therefore, this study provided evidence of the inhibitory effect of NTD and PFD on markers of pulmonary artery remodeling induced by IL-11. |
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