Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis

J Thromb Haemost. 2007 Jan;5(1):91-7. doi: 10.1111/j.1538-7836.2006.02276.x. Epub 2006 Oct 16.

Abstract

Objectives: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis.

Methods and results: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01).

Conclusion: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / enzymology
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / enzymology*
  • Carotid Artery Diseases / etiology
  • Carotid Artery, Common / diagnostic imaging*
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Interleukin-6 / blood
  • Linear Models
  • Logistic Models
  • Male
  • Matrix Metalloproteinase 1 / blood
  • Matrix Metalloproteinase 10 / blood*
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Severity of Illness Index
  • Tunica Intima / diagnostic imaging*
  • Tunica Media / diagnostic imaging*
  • Ultrasonography
  • von Willebrand Factor / metabolism

Substances

  • IL6 protein, human
  • Interleukin-6
  • von Willebrand Factor
  • Fibrinogen
  • C-Reactive Protein
  • MMP10 protein, human
  • Matrix Metalloproteinase 10
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1