On interaction of activated protein C with human aortic smooth muscle cells attenuating the secretory group IIA phospholipase A2 expression

APC inhibited the stimulated expression of sPLA2-IIA in HASMC dose-dependently (1-300 nM). At the same time, APC increased the phosphorylation of ERK 1/2 and decreased NF-κB and C/EBP-β DNA-binding activities in these cells, as compared with respective stimulated controls. Reverse transcriptase-polymerase chain reaction and cell-based ELISA reveal an endothelial protein C receptor (EPCR) expression in HASMC. Application of antibodies against EPCR and protease-activated receptor-1 (PAR-1) reduced the APC-induced ERK 1/2 activation and the treatment of cells with a PAR-1 antagonist diminished the sPLA2-IIA inhibition. The obtained results show that APC effectively suppresses the up-regulated sPLA2-IIA expression, which might contribute to the reported beneficial effects of APC in the treatment of severe inflammatory disorders.