Unravelling the effects of genetic variation in pulmonary hypertension

Investigation of a pulmonary arterial hypertension genetic locus near endothelial transcription factor SOX17

Over 9000 European people with rare diseases had their genomes sequenced as part of the UK’s BRIDGE project. One of diseases studied was pulmonary arterial hypertension (PAH) – high blood pressure in the lungs, which leads to heart failure. Dr Rhodes and his team have identified changes in a region closed to a gene called SOX17 which are more common in people with PAH compared to healthy people. SOX17 affects how blood vessels in the lung develop. In this project, they will study how these genetic changes control the SOX17 gene and whether this influences the development of PAH. They will introduce the genetic changes found near the SOX17 gene into lung blood vessel cells and investigate how they alter SOX17 function and the growth of lung blood vessels. They will also evaluate the impact of deleting SOX17 gene on the development of PAH in rats and mice. These results will help understand whether and how those genetic changes found in people with PAH contribute to the development of the disease and could help identify new treatment targets that target SOX17.