Abstract
Tissue factor (TF) is the primary initiator of the coagulation cascade. ²+ signaling is involved in TF gene expression. Monocyte chemoattractant protein-1 (MCP-1) and its receptor (CCR2) play a pivotal role in the inflammation of atherosclerosis. Although nitric oxide (NO) impairment appears to promote thrombogenicity in monocyte adhesion to endothelial cells (ECs), little is known about its mechanism. Nω-nitro-L-arginine methyl ester (L-NAME) promoted MCP-1 expression in EC culture. In response to monocyte adhesion, increased TF expression accompanied by NF-κB p65 activation was observed in L-NAME-treated ECs compared with non-treated ECs. This increased TF expression was prevented by BAPTA-AM, an intracellular ²+ chelator. Monocyte attachment to L-NAME- treated ECs increased ²+ influx compared with non-treated ECs, which was prevented by the blockade of MCP1/CCR2. These findings suggest that increased production of MCP-1 caused by L-NAME contributes to the enhancement of ²+ influx only when monocytes adhered to ECs and that this may accelerate TF expression in ECs triggered by monocyte adhesion. We demonstrate the role of ²+ influx via MCP-1/CCR2 under NO impairment in TF expression in monocyte-EC interaction.
