Inverse Regulation of MMP-9 and MMP-2 in Long-Term Follow-up After Acute Coronary Syndrome: Lack of Correlation with Platelet and Endothelial Cell Activation Markers

In atherosclerosis overactivity of matrix metalloproteinases (MMPs) is thought to contribute to plaque instability. In the present study we investigated in patients with acute coronary events: a) the longitudinal course of plasma levels of MMP-9, MMP-2 and of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), b) any association between MMPs and TIMPs with soluble markers of platelet activation (sP-selectin, sCD40L) or endothelial activation (sVCAM-1), and c) any effect of statin therapy on these parameters. Forty-one men with unstable angina pectoris (n=17) or myocardial infarction (n=24) were examined during the acute phase and nine months later. Plasma levels of MMP-9, MMP-2, TIMP-1, TIMP-2, as well as sP-selectin, sCD40L and sVCAM-1 were measured. Half of the patients from both groups received statin treatment. In the acute phase upregulation of MMP-9 and TIMP-1 and downregulation of MMP-2 was observed, congruent with the pattern of inflammatory stimulation of cells in vitro. The dysregulation of MMP-2 and TIMP-1 persisted in the chronic phase. Similarly, all cellular activation markers were upregulated in acute disease and attenuated only partly in the chronic phase, indicative of a permanent inflammatory state. Statin therapy effectively lowered lipid levels, but had no impact on MMPs or cellular activation markers. MMP-9 is a sensitive marker of acute coronary disease, whereas the continuous dysregulation of MMP-2, TIMP-1 and of cellular activation markers in both acute and chronic phases of coronary disease is indicative of persisting inflammatory stimulation. Current results fail to support a relevant anti-inflammatory effect of statins in chronic coronary disease.