Lactate dehydrogenase-induced DNA Topoisomerase 1 is a novel regulator of smooth muscle cell proliferation and remodeling in pulmonary arterial hypertension
Lifeng Jiang, Iryna Zhyvylo, Dmitry A. Goncharov, Tapan Dey, Neil J. Kelly, Leyla Teos, Lisa M. Franzi, Aisha Saiyed, Nicholas J. Kenyon, John R. Greenland, Paul J. Wolters, Stephen Y. Chan, Horace Michael DeLisser, Tatiana V. Kudryashova, Elena A. Goncharova
This study identifies LDHA-lactate-induced over-lactylation and TOP1 accumulation as drivers of PASMC hyper-proliferation and PAH, with TOP1 inhibition reversing these effects.
bioRxiv · Nov 10, 2025 · PreprintCell Biology