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Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase

Nicola Fiotti1, Michèle Emilia Moretti, Rossana Bussani

  • 1U.C.O. Clinica Medica Generale e Terapia Medica, Dipartimento di Scienze Mediche Tecnologiche e Traslazionali, Università degli Studi di Trieste, Trieste, Italy. fiotti@units.it

Atherosclerosis
|January 15, 2011
PubMed
Abstract

Insights

Matrix metalloproteinase (MMP) genetic variations impact vascular event outcomes. MMP-1 G insertion is linked to stable plaques and better prognosis, while MMP-9 variants indicate larger necrotic cores and worse outcomes.

Area of Science:

  • Cardiovascular Genetics
  • Vascular Biology
  • Biomarkers

Background:

  • Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix remodeling, influencing plaque stability and vascular event pathogenesis.
  • Genetic polymorphisms in MMP genes may alter protein expression and function, potentially impacting individual susceptibility to cardiovascular diseases.

Purpose of the Study:

  • To investigate the association between specific matrix metalloproteinase (MMP) genetic polymorphisms and the vulnerability of carotid plaques.
  • To evaluate the correlation of these MMP genetic polymorphisms with the clinical outcomes of acute vascular events, including stroke and acute coronary syndromes.

Main Methods:

  • Genotyping of MMP-1 (-1607 G in/del), MMP-3 (-1171 A in/del), and MMP-9 microsatellite ((13-26) CA repeats) polymorphisms was performed.
  • The study included 204 patients with cerebrovascular disease (CVD) and 208 patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI).
  • Plaque vulnerability features and clinical outcomes (stroke, MACE) were assessed in relation to MMP genotypes.

Main Results:

  • MMP-1 G insertion carriers exhibited smaller plaques with thicker fibrous caps, significantly reduced stroke risk (OR 0.27), and lower risk of Major Adverse Cardiac Events (MACE) (OR 0.22) in UA/NSTEMI patients.
  • No significant associations were found for MMP-3 polymorphisms with plaque features or clinical outcomes.
  • MMP-9 variants with ≥22 CA repeats were associated with larger plaques, increased lipid core, higher stroke risk (OR 2.2), and significantly elevated MACE risk (OR 4.1) in UA/NSTEMI patients.

Conclusions:

  • The MMP-1 G insertion polymorphism is associated with more stable carotid plaques and a favorable prognosis in acute vascular events.
  • Conversely, MMP-9 variants with ≥22 repeats are linked to larger necrotic cores and a poorer prognosis in patients experiencing UA/NSTEMI.
  • MMP genetic polymorphisms serve as potential predictive markers for vascular plaque vulnerability and clinical outcomes.

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