Rehab Alharbi, Merve Keles, Nadia Fernandes, Hannah Maude, Adam Fellows, Richard D. Williams, Chien-Nien Chen, Nathalie Lambie, Nik Matthews, May Al-Sahaf, Sam N. Barnett, Minzhe Guo, Lan Zhao, Allan Lawrie, Jeffrey A. Whitsett, Inês Cebola, Beata Wojciak-Stothard
Imperial College London. University of Hafr Al Batin. Hammersmith Hospital. Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine.
United Kingdom, Saudi Arabia and United States
Communications Biology
Commmun Biol 2026;
DOI: 10.1038/s42003-026-10493-5
Abstract
Pulmonary arterial hypertension (PAH) is a severe, currently incurable lung disease characterized by endothelial injury and excessive repair, leading to arterial narrowing. However, the contributory mechanisms remain poorly understood. Here we show that Krüppel-like factor 6 (KLF6) is a feature of vascular pathology in PAH. KLF6 expression is elevated in human PAH and preclinical models of PAH and promotes endothelial repair and angiogenesis through transcriptomic remodelling, with effects distinct from those of KLF2 and KLF4. Endothelial KLF6 also stimulates vascular smooth muscle cell proliferation, which is attenuated by bosentan and imatinib. DisGeNET and spatial transcriptomic analyses of control and PAH lungs reveal elevated KLF6 in PAH endothelium, endothelial progenitor cells, and PAH with alveolar capillary dysplasia. In summary, KLF6 activation uniquely orchestrates endothelial repair and is a feature of the angio-proliferative vascular phenotype in PAH.
Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes