Pulmonary arterial hypertension (PAH) is a deadly disease that narrows the tiny arteries in the lungs, forcing the heart to work harder and often leading to failure. Current drugs mainly relax blood vessels but do not stop the underlying cell growth that drives the disease. A new study led by Chen Lihong (East China Normal University) and Yang Guangrui (Shanghai University of Medicine \u0026 Health Sciences) reveals a different approach: turning on a “clock‑gene” called REV‑ERBα. Using several mouse models, the researchers showed that mice lacking REV‑ERBα develop worse PAH, while boosting the gene—either with a drug that activates it or by delivering extra copies via a harmless virus—significantly improves lung artery health. Importantly, the drug still worked when given after the disease was already established, suggesting a wider therapeutic window than previously thought. The benefit comes from REV‑ERBα’s ability to shut down a protein called BNIP3, which otherwise triggers excessive removal of mitochondria (the cell’s power plants) in smooth‑muscle cells of the pulmonary artery. By preserving mitochondrial function, the cells stop proliferating uncontrollably and the vessels remodel less. These findings point to a novel, circadian‑rhythm‑based strategy for PAH that could complement existing vasodilator therapies and offer hope for patients with advanced disease.
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