Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability.

Plaque destabilization leading to myocardial infarction is observed after surgery even if the intervention is of noncardiovascular nature. Mediators of peri- or postoperative stress responsible for such events could include catecholamines and lipopolysaccharide (LPS). Monocytes may be involved in destabilization of atherosclerotic plaques by production of matrix metalloproteinases (MMP). We examined whether catecholamines could affect the expression of MMPs in human monocytes/macrophages and whether catecholamines could modulate LPS-stimulated expression of particular MMPs in these cells. Epinephrine and norepinephrine up-regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral blood monocytes and monocyte-derived macrophages. We further characterized this effect employing the monocytic cell line U937 and showed that catecholamines potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA levels of the respective MMPs also increased. These effects did not result from higher mRNA stability but rather from increased transcription possibly induced by enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2-receptors. If this mechanism is also effective in vivo, our findings might, at least in part, help to explain the observation that cardiac events are important causes of morbidity and mortality after noncardiac surgery and support the findings that peri-operative beta-blockade has been shown to reduce postoperative mortality from cardiac events.