When Cells Sense Pressure: New Mechanism Discovered in Pulmonary Hypertension

An international research team led by DZL scientists Dr. Fenja Knoepp and Prof. Dr. Serge Adnot from Justus Liebig University Giessen (DZL site UGMLC) as well as Prof. Dr. Eric Honoré has uncovered a key mechanism involved in the development of pulmonary hypertension. The study, published in the prestigious journal Circulation Research, identifies the mechanosensitive ion channel Piezo1 in the smooth muscle cells of the pulmonary arteries (PASMCs) as a major contributor to this currently incurable and life-threatening lung disease.

Particularly noteworthy: the study also reveals that Piezo1 in PASMCs promotes cellular ageing processes, known as senescence, particularly in the endothelial cells that form the inner lining of blood vessels. Such senescent cells stop dividing but emit pro-inflammatory signals and thus contribute significantly to pathological changes in the pulmonary vasculature.

Using precise genetic techniques to deactivate Piezo1 specifically in PASMCs of PH disease models, the scientists observed a marked reduction in hypoxia-induced vessel-narrowing, pathological remodelling processes, and the number of harmful senescent cells. As a result, the structure of the pulmonary vessels improved significantly - and thus effectively prevented against the development of pulmonary hypertension.

These findings highlight Piezo1 in PASMCs as a key player in the development of pulmonary hypertension and suggests a promising new therapeutic avenue. Targeting Piezo1 could help curb disease progression and offer hope for patients suffering from this severe condition.

The resarch team: Dr. Fenja Knoepp, Prof. Dr. Eric Honoré und Prof. Dr. Serge Adnot.

Original publication: Fenja Knoepp et al.: Piezo1 in PASMCs: Critical for Hypoxia-Induced Pulmonary Hypertension Development. Circulation Research. 2025;136:1031–1048. https://doi.org/10.1161/CIRCRESAHA.124.325475