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Updated: Oct 9, 2025
Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models
Published on: June 20, 2025
Vardenafil Activity in Lung Fibrosis and In Vitro Synergy with Nintedanib
Michael H Bourne1, Theodore J Kottom1, Deanne M Hebrink1
1Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, 8-24 Stabile, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Idiopathic pulmonary fibrosis (IPF) remains an intractably fatal disorder, despite the recent advent of anti-fibrotic medication. Successful treatment of IPF, like many chronic diseases, may benefit from the concurrent use of multiple agents that exhibit synergistic benefit. In this light, phosphodiesterase type 5 inhibitors (PDE5-Is), have been studied in IPF primarily for their established pulmonary vascular effects. However, recent data suggest certain PDE5-Is, particularly vardenafil, may also reduce transforming growth factor beta 1 (TGF-β1) activation and extracellular matrix (ECM) accumulation, making them a potential target for therapy for IPF. We evaluated fibroblast TGF-β1-driven extracellular matrix (ECM) generation and signaling as well as epithelial mesenchymal transformation (EMT) with pretreatment using the PDE5-I vardenafil. In addition, combinations of vardenafil and nintedanib were evaluated for synergistic suppression of EMC using a fibronectin enzyme-linked immunosorbent assay (ELISA). Finally, the effects of vardenafil on fibrosis were investigated in a bleomycin mouse model. Our findings demonstrate that vardenafil suppresses ECM generation alone and also exhibits significant synergistic suppression of ECM in combination with nintedanib in vitro. Interestingly, vardenafil was shown to improve fibrosis markers and increase survival in bleomycin-treated mice. Vardenafil may represent a potential treatment for IPF alone or in combination with nintedanib. However, additional studies will be required.
Insights
Vardenafil, a PDE5 inhibitor, shows promise in treating idiopathic pulmonary fibrosis (IPF). It suppresses extracellular matrix (ECM) generation alone and synergistically with nintedanib, improving fibrosis in mice.
Area of Science:
- Pulmonology
- Pharmacology
- Fibrosis Research
Background:
- Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited treatment options.
- Current treatments may benefit from combination therapies for synergistic effects.
- Phosphodiesterase type 5 inhibitors (PDE5-Is) are explored for IPF beyond their vascular effects.
Purpose of the Study:
- To evaluate vardenafil's effect on fibroblast extracellular matrix (ECM) generation and epithelial-mesenchymal transformation (EMT).
- To assess the synergistic effect of vardenafil combined with nintedanib on ECM accumulation.
- To investigate vardenafil's efficacy in a bleomycin-induced mouse model of lung fibrosis.
Main Methods:
- In vitro studies using fibroblasts treated with vardenafil to assess ECM generation and signaling.
- Fibronectin enzyme-linked immunosorbent assay (ELISA) to evaluate synergistic ECM suppression by vardenafil and nintedanib.
- In vivo experiments using a bleomycin mouse model to assess vardenafil's antifibrotic effects and survival.
Main Results:
- Vardenafil alone suppressed fibroblast-driven ECM generation in vitro.
- Vardenafil demonstrated significant synergistic suppression of ECM when combined with nintedanib.
- Vardenafil treatment improved fibrosis markers and increased survival in bleomycin-treated mice.
Conclusions:
- Vardenafil exhibits potential as a therapeutic agent for IPF, both as a monotherapy and in combination with nintedanib.
- The findings suggest vardenafil's ability to reduce ECM accumulation and mitigate fibrosis progression.
- Further research is warranted to confirm vardenafil's efficacy and safety in clinical settings for IPF treatment.
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