Tissue factor induces human coronary artery smooth muscle cell motility through Wnt-signalling

Tissue factor (TF) is the most relevant physiological trigger of thrombosis contributing to the presentation of clinical ischemic events after plaque rupture. However, the role of human vascular smooth muscle cell (HVSMC) TF in vascular remodeling, restenosis and atherosclerosis is less known. We have hypothesized that TF contributes to atherosclerotic lesion formation, triggering smooth muscle cell migration through a specific yet unknown signaling pathway.

The aim of this study has been to investigate the signal transduction mechanism by which TF may contribute to the transition of resident static contractile HVSMC into a migrating cell that promotes atherosclerotic plaque progression.

We have used a system biology discovery approach with gene-engineered HVSMCs to identify genes/proteins involved in the TF-triggered effects in HVSMC obtained from the coronary arteries of human adult hearts.

Analysis of wild-type HVSMC (TF(+) ) and TF(-) silenced HVSMC (TF(-) ) showed that TF is involved in the regulation of Wnt signaling and in the expression of downstream proteins that affect the atherosclerotic process.

The 'in silico' analysis pointed to specific Wnt-pathway proteins that have been validated in cell culture and also have been found expressed in human advanced atherosclerotic plaques but not in early lesions. TF signals through Wnt to regulate coronary smooth muscle cell migration and vascular remodeling.