Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals

Yasmin, Carmel M. McEniery, Kevin M. O'Shaughnessy, Patrick Harnett, Asif Arshad, Sharon Wallace, Kaisa Maki-Petaja, Barry McDonnell, Mike J. Ashby, John Brown, John R. Cockcroft, Ian B. Wilkinson

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86 Citations (Scopus)

Abstract

BACKGROUND - Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS - Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that ≈60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS - We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.

Original languageEnglish
Pages (from-to)1799-1805
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Aortic pulse wave velocity
  • Augmentation index
  • MMP-9 gene polymorphisms
  • MMP-9 levels
  • Serum elastase activity

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