European Heart Journal Advance Access published online on March 5, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm003
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Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study
1 Department of Vascular Surgery, St George's Hospital Medical School, London, UK
2 Department of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, University of Leicester, Leicester LE2 7LX, UK
Received 8 November 2006; revised 3 February 2006; accepted 9 February 2007.
* Corresponding author. Tel: +44 116 252 3125; fax: +44 116 252 3108. E-mail address: is11{at}le.ac.uk
Aims: To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (ECG) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man.
Methods and results: Plasma MMP-2 and MMP-9 were assayed at intervals (0–12, 12–24, 24–48, 48–72, 72–96, and >96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. ECG assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138–262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005–0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0–12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to <0.001) and neutrophil count (P = 0.014 to <0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively).
Conclusion: Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.
Key Words: Matrix metalloproteinase • Myocardial infarction • Remodelling
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