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

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 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

White AJ,Duffy SJ,Walton AS,Ng JF,Rice GE,Mukherjee S,Shaw JA,Jennings GL,Dart AM,Kingwell BA

doi

10.1016/j.cardiores.2007.05.003

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

813-20

issue

4

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(07)00216-7

journal_volume

75

pub_type

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