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Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease

Anthony J White1, Stephen J Duffy, Anthony S Walton

  • 1Baker Heart Research Institute and The Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.

Cardiovascular Research
|June 5, 2007
PubMed

Insights

The MMP-3 6A allele is linked to unstable coronary syndromes. This genetic variant promotes plaque buildup and outward vessel remodeling, increasing heart attack risk.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Biomarkers in Atherosclerosis

Background:

  • Matrix metalloproteinases (MMPs) are implicated in cardiovascular disease.
  • The MMP-3 gene polymorphism (-1171, 5A/6A) is a potential predictor of unstable coronary syndromes.
  • Understanding genetic predispositions can aid in risk stratification for coronary artery disease (CAD).

Purpose of the Study:

  • To investigate the association between the MMP-3 polymorphism (-1171, 5A/6A) and coronary plaque characteristics.
  • To determine if this polymorphism predicts unstable clinical presentation in patients with coronary artery disease.

Main Methods:

  • Coronary intravascular ultrasound and angiography were used to assess plaque burden and stenosis in 40 de novo CAD patients.
  • Patients were categorized into unstable coronary syndrome (n=19) or stable angina pectoris (n=21).
  • A validation cohort (n=161) and the total population (n=201) were analyzed to confirm findings.

Main Results:

  • The MMP-3 6A allele was significantly more prevalent in patients with unstable coronary syndromes (p=0.027).
  • 6A allele carriers exhibited greater plaque burden, positive coronary remodeling, and higher plasma MMP-3 concentrations.
  • This association remained significant and independent of conventional risk factors in validation and total cohorts (p=0.007).

Conclusions:

  • The MMP-3 6A allele is associated with positive coronary remodeling and increased plaque burden.
  • Carrying the 6A allele increases susceptibility to unstable coronary syndromes in humans.
  • This polymorphism serves as a potential genetic marker for predicting adverse cardiovascular events.
Abstract

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