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

White, Anthony J., Duffy, Stephen J., Walton, Anthony S., Ng, Jer Fuu, Rice, Gregory E., Mukheriee, Swati, Shaw, James A., Jennings, Garry L., Dart, Anthony M. and Kingwell, Bronwyn A. (2007) Matrix metalloproteinase-3 and coronary remodelling: Implications for unstable coronary disease. Cardiovascular Research, 75 4: 813-820. doi:10.1016/j.cardiores.2007.05.003


Author White, Anthony J.
Duffy, Stephen J.
Walton, Anthony S.
Ng, Jer Fuu
Rice, Gregory E.
Mukheriee, Swati
Shaw, James A.
Jennings, Garry L.
Dart, Anthony M.
Kingwell, Bronwyn A.
Title Matrix metalloproteinase-3 and coronary remodelling: Implications for unstable coronary disease
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 0008-6363
1755-3245
Publication date 2007-09
Sub-type Article (original research)
DOI 10.1016/j.cardiores.2007.05.003
Volume 75
Issue 4
Start page 813
End page 820
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Objectives: Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (– 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation.
Methods and results: Forty patients with de novo presentation of coronary artery disease (CAD) were classified into unstable coronary syndrome (n=19) or stable angina pectoris (n=21). On coronary intravascular ultrasound, patients with unstable disease had a greater plaque burden, more positive (outward) coronary remodelling, and all but one were MMP-3 6A allele carriers (p=0.027 compared with stable). The relationship between the 6A allele and unstable presentation was substantiated in a validation cohort of 161 CAD patients (58 stable and 103 unstable) and in the total population of 201 CAD patients (79 stable and 122 unstable, p=0.007), and was independent of conventional risk factors. Furthermore, 6A allele carriers had a higher plasma MMP-3 concentration (15.8±12.5 versus 11.7±7.2 ng/mL, p=0.01), maximum coronary stenosis on angiography (89±15% versus 80±23%, p=0.02), plaque area (12.0±5.2 versus 7.5±3.6 mm2, p=0.03), percentage plaque burden (82±7 versus 71±13%, p=0.003), and remodelling ratio (1.03±0.23 versus 0.83±0.12, p=0.003).
Conclusions: The MMP-3 6A allele promotes positive coronary remodelling, greater plaque burden, and increased susceptibility to unstable coronary syndromes in humans.
Keyword Matrix metalloproteinase
Acute coronary syndrome
Vulnerable plaque
Arterial remodelling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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