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Updated: Jul 18, 2026

A Murine Model of Carotid Aneurysm Formation
03:47

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Published on: September 9, 2025

Genes predisposing to rapid aneurysm growth.

J T Powell1

  • 1Imperial College, Charing Cross Campus, St. Dunstan's Rd., London W6 8RP, UK. j.powell@imperial.ac.uk

Annals of the New York Academy of Sciences
|December 22, 2006
PubMed
Summary

Genetic variations in matrix metalloproteinase (MMP) genes did not significantly impact small abdominal aortic aneurysm growth. However, specific plasminogen activator inhibitor-1 (PAI-1) genotypes were linked to faster aneurysm expansion.

Area of Science:

  • Vascular Biology
  • Genetics
  • Cardiovascular Research

Background:

  • Abdominal aortic aneurysms (AAAs) are a significant cause of mortality.
  • Understanding genetic factors influencing AAA growth is crucial for risk stratification.
  • Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs, PAI-1) are implicated in AAA pathogenesis.

Purpose of the Study:

  • To investigate the association between functional polymorphisms in MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, and PAI-1 genes and the growth rate of small abdominal aortic aneurysms.
  • To determine if specific genetic variations predict accelerated AAA expansion.

Main Methods:

  • Analysis of functional polymorphisms in MMP-2, MMP-3, MMP-9, MMP-12, TIMP-1, and PAI-1 genes.
  • Recruitment of patients from the U.K. Small Aneurysm Trial surveillance cohort.

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  • Calculation of mean linear aneurysm growth rates using flexible modeling over a mean follow-up of 2.6 years.

    • Main Results:

    • No significant associations were found between polymorphisms in MMP-2, MMP-3, MMP-9, MMP-12, and TIMP-1 genes and AAA growth rates.
    • Patients with the 5G5G PAI-1 genotype showed borderline significantly increased growth rates (P=0.06).
    • PAI-1 haplotype analysis revealed significantly faster aneurysm growth in 5G5G/GG patients (mean 0.46 mm/year faster).

    Conclusions:

    • Specific MMP gene polymorphisms do not appear to significantly influence small AAA growth.
    • The plasminogen system, specifically PAI-1, plays a small but potentially clinically significant role in AAA growth.
    • PAI-1 genotype may serve as a predictive marker for AAA expansion rate.