Plasminogen activator inhibitor-1 from bone marrow-derived cells suppresses neointimal formation after vascular injury in mice

Arteriosclerosis, Thrombosis, and Vascular Biology
K SchäferS Konstantinides

Abstract

To investigate the ability of bone marrow (BM)-derived cells to modulate neointimal growth after injury by expressing plasminogen activator inhibitor-1 (PAI-1). We performed BM transplantation (BMT) in lethally irradiated wild-type (WT) and PAI-1(-/-) mice. Three weeks after carotid injury with ferric chloride, analysis of Y-chromosome DNA expression in the vessel wall of female hosts revealed that 20.8+/-6.0% of the cells in the neointima and 37.6+/-5.7% of those in the media were of BM origin. Lack of PAI-1 in either the host or the donor cells did not affect recruitment of BM-derived cells into sites of vascular injury. The neointima consisted predominantly of smooth muscle cells, and a proportion of these cells expressed PAI-1. Overall, lack of PAI-1 was associated with enhanced neointimal formation. However, importantly, BMT(WT-->PAI-1(-/-)) mice exhibited reduced neointimal area (P=0.05) and luminal stenosis (P=0.04) compared with BMT(PAI-1(-/-)-->PAI-1(-/-)) mice. Although PAI-1-expressing cells were shown to be present in BMT(WT-->PAI-1(-/-)) lesions, these mice did not exhibit detectable levels of the inhibitor in the circulation, suggesting that local production of PAI-1 by cells in the neointima and media was suffici...Continue Reading

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Citations

May 17, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Yan JiWilliam P Fay
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