Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology

Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, and is driven by molecular and cellular mechanisms described in the hallmarks of aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, also mediates processes like vascular stiffness, cellular senescence, and immune evasion. This review highlights PAI-1's role in cardiovascular aging with a special emphasis on senescence, a key hallmark of aging. It further explores PAI-1's therapeutic potential, with a focus on its contribution to ECM remodeling, senescence signaling, and immune checkpoint regulation. Targeting PAI-1 could provide a promising strategy to mitigate age-related cardiovascular disease.