Differential modulation of the sGC-cGMP pathway by sGC stimulators and activators in human lung cells - PubMed
4 days ago
- #sGC-cGMP pathway
- #oxidative stress
- #chronic lung diseases
- Chronic lung diseases involve oxidative stress, inflammation, and fibroproliferation, impairing NO-sGC-cGMP signaling.
- Study compared sGC stimulator (riociguat) and sGC activator (cinaciguat), with/without PDE5 inhibitor sildenafil, in human lung cells exposed to cigarette smoke extract (CSE).
- COPD and asthma patients' lung tissue showed reduced sGC α1 and β1 expression; CSE oxidized sGC heme group, reducing responsiveness to NO and riociguat.
- Cinaciguat maintained cGMP production under oxidative stress, unlike riociguat; sildenafil enhanced cGMP levels for both drugs.
- Cinaciguat and riociguat reduced CSE-induced oxidative stress, inflammation, and profibrotic gene expression in epithelial cells, fibroblasts, neutrophils, and endothelial cells.
- Cinaciguat, especially with sildenafil, showed stronger effects across endpoints compared to riociguat.
- Findings highlight distinct pharmacodynamic profiles of sGC stimulators vs. activators under oxidative stress, supporting sGC modulation as a therapy for chronic lung diseases.