Progranulin deficiency induces premature vascular senescence and dysfunction

American Journal of Physiology-Heart and Circulatory Physiology 2026 Open access

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Authors: Renata de Azevedo Melo Luvizotto, André Ferreira do Nascimento, Gustavo F Pimenta, Rafael M Costa, Tyler Beling, Shubhnita Singh, Juliano Vilela Alves, Wanessa Awata, Angela Russ, Adeyeye I. Haastrup, Rolando Cuevas, Parya Behzadi
+4 more Cynthia St Hilaire, Justin Roberts, Ariane Bruder, Thiago Bruder-Nascimento
DOI: 10.1152/ajpheart.00012.2026
Cited by: 1
References: 43

Abstract

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.

Fields of Study & Subjects

Amyotrophic Lateral Sclerosis Research Telomeres Telomerase and Senescence Cerebrovascular and genetic disorders

Publication details

Journal / source
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Volume
331
Issue
1
Pages
H260–H275
Publication date
3 June 2026
Language
EN