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October 1, 2025Journal of Clinical InvestigationOpen Access

Plasminogen Activator Inhibitor-1 promotes aortic aging-like pathophysiology in humans and mice

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Authors

AKAlireza KhoddamAKAnthony KalousdianMEMesut Eren

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Overview

Mouse model analysis shows PAI-1 promotes cardiovascular aging and related pathologies in humans, suggesting intervention potential.

Key Points

  • Reduction in PAI-1 in mice was linked to 20% longer lifespan and improved cardiovascular function despite stress.
  • Mice with PAI-1 overexpression showed accelerated cardiovascular aging evidenced by worsened systolic hypertension.
  • Single cell transcriptomics indicated a protective mechanism in aortas of Serpine1TA700/+ mice through extracellular matrix regulation.
  • Inhibition of PAI-1 reversed aging-related vascular changes and normalized systolic blood pressure in stressed mice.

Cite This Study

Khoddam et al. (2025) studied this question.

synapsesocial.com/papers/68dd91d5fe798ba2fc498f84https://doi.org/10.1172/jci196714
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract Fri020: Plasminogen Activator Inhibitor-1 Governs Vascular Aging2025
  2. 2Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice2025
  3. 3Angiotensin-Converting Enzyme 2 Overexpression Protects Heart from Aging-Induced Injury in C57BL/6 Mice2026
  4. 4Inflammatory Macrophage-derived Plasminogen Activator Inhibitor-1 Exacerbates Inflammation through Efferocytosis Inhibition2025
  5. 5A Contemporary Review of PAI-1: Structure/Function, Genetic Architecture, and Intracellular/Extracellular Roles2025