Microparticles from apoptotic vascular smooth muscle cells induce endothelial dysfunction, a phenomenon prevented by beta3-integrin antagonists.

Fragile atherosclerotic plaques are rich in apoptotic smooth muscle cells (SMCs) and macrophages, generating microparticules (MPs) which accumulate locally and may be released in blood in case of mechanical or spontaneous plaque disruption. Besides being highly procoagulant, this material may interact with downstream endothelium. Using a model of mouse aorta vaso-reactivity, we have investigated the effects of apoptotic MPs prepared in vitro from Fas-ligand sensitive SMCs.

Shedding of active tissue factor by aortic smooth muscle cells (SMCs) undergoing apoptosis.

As apoptosis of neo-intimal SMCs is a feature of advanced atherosclerotic plaques, the procoagulant properties of SMCs of synthetic phenotype undergoing apoptosis were investigated. SMCs isolated from rat aorta obtained 10 days after balloon injury, previously found to up-regulate Tissue Factor (TF) and Tissue Factor Inhibitor (TFPI) and to release large amounts of TFPI (Ghrib et al. Thromb Haemost 2002;87:1043-50), were sensitive to the apoptosis induced by Fas-ligand.

The expression of tissue factor and tissue factor pathway inhibitor in aortic smooth muscle cells is up-regulated in synthetic compared to contractile phenotype.

Tissue factor (TF) and its specific inhibitor TF pathway inhibitor (TFPI) are produced by vascular smooth muscle cells (SMCs) in vitro and are increased in vivo in atherosclerotic compared to normal vessels. Besides local regulation of the hemostatic balance, this may be related to non-hemostatic TF/protease dependent functions such as SMC proliferation, adhesion and migration. The aim of the study was to compare the expression of both proteins between the contractile (normal adult) and synthetic (neo-intimal) SMC phenotypes.