Renata de Azevedo Melo Luvizotto, André Ferreira do Nascimento, Gustavo F Pimenta, Rafael M Costa, Tyler Beling, Shubhnita Singh, Juliano Alves, Wanessa Awata, Angela Russ, Adeyeye Haastrup, Rolando Cuevas, Parya Behzadi, Cynthia St Hilaire, Justin Roberts, Ariane Bruder, Thiago Bruder-Nascimento
This study identifies progranulin (PGRN) as a key regulator of premature vascular dysfunction. Using human and mouse arteries and integrated multi-omics analyses, we show that PGRN deficiency induces early vascular senescence, mitochondrial dysfunction, epigenetic remodeling, and fibrosis. Senolytic treatment uncovers divergent roles of endothelial versus smooth muscle cell senescence in vascular function, highlighting PGRN as an important modulator of vascular homeostasis during aging.