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


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 mm(2), 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.
White
Anthony J
AJ
Baker Heart Research Institute and The Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.
Duffy
Stephen J
SJ
Walton
Anthony S
AS
Ng
Jer Fuu
JF
Rice
Gregory E
GE
Mukherjee
Swati
S
Shaw
James A
JA
Jennings
Garry L
GL
Dart
Anthony M
AM
Kingwell
Bronwyn A
BA
D000368:Aged; D000704:Analysis of Variance; D000789:Angina, Unstable / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D016002:Discriminant Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D018084:Ultrasonography, Interventional
D005819:Genetic Markers; D019278:Matrix Metalloproteinase 3