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

Alireza Khoddam1, Douglas Vaughan1, Lisa Wilsbacher1

  • 1Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, USA.

The Journal of Cardiovascular Aging
|February 23, 2026
PubMed

Insights

Plasminogen activator inhibitor-1 (PAI-1) drives cardiovascular aging and senescence. Targeting PAI-1 offers a promising therapeutic strategy to combat age-related cardiovascular diseases and vascular dysfunction.

Area of Science:

  • Cardiovascular biology
  • Aging research
  • Molecular medicine

Background:

  • Cardiovascular aging contributes to heart failure and vascular dysfunction.
  • Hallmarks of aging involve molecular and cellular mechanisms.
  • Plasminogen activator inhibitor-1 (PAI-1) regulates fibrinolysis, vascular stiffness, senescence, and immune evasion.

Purpose of the Study:

  • To review the role of PAI-1 in cardiovascular aging, focusing on senescence.
  • To explore the therapeutic potential of targeting PAI-1.

Main Methods:

  • Literature review focusing on PAI-1's involvement in aging processes.
  • Analysis of PAI-1's contribution to extracellular matrix remodeling, senescence signaling, and immune checkpoint regulation.

Main Results:

  • PAI-1 is implicated in key aging hallmarks, particularly cellular senescence.
  • PAI-1 influences extracellular matrix remodeling and immune responses relevant to aging.

Conclusions:

  • PAI-1 plays a significant role in cardiovascular aging.
  • Targeting PAI-1 presents a potential therapeutic avenue for mitigating age-related cardiovascular diseases.

Keywords:
Cardiovascular diseaseagingsenescencevascular biology

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