Complement activation, indicated by the elevation of C5a, seems to be associated with increased cardiovascular risk in patients with advanced atherosclerosis. Clinically, determination of C5a may add to the predictive value of other non-specific inflammatory parameters.

We have recently shown that resting human mast cells (MCs) produce tissuetype plasminogen activator (t-PA) without simultaneously expressing plasminogen activator inhibitor 1 (PAI-1). In the present study we have identified the anaphylatoxin rhC5a as a potent inducer of PAI-1 expression in human MCs and basophils. In primary human skin MCs and primary blood basophils, exposure to rhC5a was followed by an increase from undetectable to significant levels of PAI-

1 The results of several clinical studies investigating the e ect of statin therapy on the ®brinolytic system in vivo are inconclusive. We compared the e ect of six di erent statins (atorvastatin, cerivastatin,¯uvastatin, lovastatin, pravastatin, simvastatin) on components of the ®brinolytic system expressed by human vascular endothelial cells and smooth muscle cells and by the human hepatoma cell line HepG2. 2 All statins used except pravastatin signi®cantly decreased PAI-1 production in human endothelial and smooth muscle cells. This e ect was also seen in the presence of IL-1a and TNF-a. All statins except pravastatin increased t-PA production in human smooth muscle cells. On a molar basis cerivastatin was the most e ective HMG CoA reductase inhibitor used. Only simvastatin and lovastatin increased t-PA production in endothelial cells. The e ects on the ®brinolytic system were reversed by mevalonate. Statins decreased mRNA levels for PAI-1 in endothelial and smooth muscle cells and increased mRNA levels for t-PA in smooth muscle cells. Statins did not a ect PAI-1 expression in HepG2 cells. Cell viability was not in¯uenced by statins in endothelial cells and HepG2 cells whereas in smooth muscle cells a cytotoxic e ect was seen at high concentrations.3 If the e ects on the ®brinolytic system of vascular cells in vitro shown in this study are also operative in vivo one could speculate that by increasing t-PA and decreasing PAI-1 at sites of vascular lesions statins might reduce ®brin formation and thrombus development. Such an e ect might contribute to the clinically proven bene®ts of statin therapy.

sFAS is an independent risk predictor in advanced HF patients. It may be of particular value for the identification of high-risk patients in addition to BNP. Conversely, sTRAIL appears to be protective and could be an interesting therapeutic agent.