Plasminogen activator inhibitor 1 promotes aortic aging-like pathophysiology in humans and mice.

ABSTRACT: Plasminogen activator inhibitor 1 (PAI-1), encoded by SERPINE1, contributes to age-related cardiovascular disease (CVD) and other aging-related pathologies. Humans with a heterozygous loss-of-function SERPINE1 variant exhibit protection against aging and cardiometabolic dysfunction. We engineered a mouse model mimicking the human mutation (Serpine1TA700/+) and compared cardiovascular responses with WT littermates. Serpine1TA700/+ mice lived 17% longer than did littermate control mice. Under l-NG-nitro-arginine methyl ester-induced (l-NAME-induced) vascular stress, Serpine1TA700/+ mice exhibited diminished pulse wave velocity (PWV), lower systolic blood pressure (SBP), and preserved left ventricular diastolic function compared with controls. Conversely, PAI-1-overexpressing mice had measure

SUBMITTER: Khoddam A 

PROVIDER: S-EPMC12646655 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature