Key result
Reduced frataxin expression leads to endothelial cell senescence in pulmonary hypertension, and targeting these cells with the senolytic drug Navitoclax effectively reversed established disease in experimental models.
Targeting endothelial cell senescence with senolytic drugs represents a promising new therapeutic strategy for multiple forms of pulmonary hypertension beyond Group 1 and 4.
Pulmonary hypertension (PH), increased blood pressure within the lungs, is classified into five diagnostic groups based on etiology, with treatment assigned on this basis. Currently, only Group 1 pulmonary arterial hypertension (PAH) and Group 4 chronic thromboembolic PH (CTEPH) have pharmacological treatments available. The role of the endothelial cell in pulmonary hypertension has long been debated, and in this issue of the JCI, Culley et al. present evidence for the reduction in frataxin expression across multiple groups of PH. Reduced frataxin expression led to endothelial cell senescence and associated with the development of PH. Removal of the senescent cells using the senolytic drug Navitoclax in multiple models of PH effectively treated PH, suggesting a new class of treatments that may work beyond Group 1 and Group 4 PH in patients with evidence of pulmonary vascular endothelial senescence.
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Lawrie et al. (2021) conducted an editorial in Pulmonary hypertension. Navitoclax was evaluated. Reduced frataxin expression leads to endothelial cell senescence in pulmonary hypertension, and targeting these cells with the senolytic drug Navitoclax effectively reversed established disease in experimental models.
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