Pulmonary vascular disease & thromboembolism
Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies
Authors' conclusion
These findings establish α5β1 integrin as a pivotal driver of PAH pathology
Study context
- Population
- Pulmonary arteries (PAs), PA smooth muscle cells and PA endothelial cells from patients with pulmonary arterial hypertension (PAH) and controls; Sugen/hypoxia and monocrotaline rat models; human precision-cut lung slices
- Comparison
- α5β1 integrin inhibition vs standard of care and sotatercept
Methodological detailsmulticentre, preclinical, external CRO validation
- Multicentre
- Preclinical
- External CRO validation
Main finding
As reported in the abstract
- Integrin α5β1 upregulated in PA endothelial cells and PA smooth muscle cells from patients with PAH and in remodeled PAs from animal models
- α5β1 blockade or α5 depletion downregulated FOXM1-regulated gene networks, causing mitotic defects and inhibiting the pro-proliferative, apoptosis-resistant phenotype of PAH cells
- α5β1 blockade attenuated pulmonary vascular remodeling and improved hemodynamics and RV function, matching or exceeding standard of care and sotatercept in multiple preclinical models
- Ex vivo: potential to reverse advanced remodeling in human precision-cut lung slices
Original publication
Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies. Circulation. Published 20 January 2025. doi:10.
Summarised from the published abstract; every number is checked against it