NIH R01 · 2024
Background: Endothelial cell (EC) pathobiology drives pulmonary hypertension (PH), but confusion over the evolution of EC phenotypes in this disease has persisted for decades. EC senescence, a state of stable cell cycle arrest, has been reported in PH, but the regulatory features are unknown. Led by our prior work showing deficiency of iron-sulfur (Fe-S) clusters in PH, we found that a Fe-S biogenesis protein, frataxin (FXN), controls senescence in pulmonary ECs. This may occur in Friedreich’s ataxia (FRDA), a disease marked by genetic FXN deficiency, cardiomyopathy, and often PH. Here, we offer a new model of EC biology in PH, where FXN loss promotes genotoxic stress and senescence in a…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.