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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1254.)
© 2006 American Heart Association, Inc.

Vascular Biology

Plasminogen Activator Inhibitor-1 From Bone Marrow–Derived Cells Suppresses Neointimal Formation After Vascular Injury in Mice

Katrin Schäfer; Marco R. Schroeter; Claudia Dellas; Miriam Puls; Mirko Nitsche; Elisabeth Weiss; Gerd Hasenfuss; Stavros V. Konstantinides

From the Department of Cardiology and Pulmonology (K.S., M.R.S., C.D., M.P., G.H., S.V.K.), Georg August University School of Medicine, Goettingen, Germany; and Department of Radiotherapy and Radiooncology (M.N., E.W.), Georg August University School of Medicine, Goettingen, Germany.

Correspondence to Katrin Schäfer, MD, Associate Professor of Medicine, Department of Cardiology and Pulmonology, Georg August University School of Medicine, D-37099 Goettingen, Germany. E-mail kschaefer{at}med.uni-goettingen.de

Objective— To investigate the ability of bone marrow (BM)–derived cells to modulate neointimal growth after injury by expressing plasminogen activator inhibitor-1 (PAI-1).

Methods and Results— 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^{WTPAI-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^{WTPAI-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 sufficient to reduce luminal stenosis.

Conclusions— PAI-1 from BM-derived cells appears capable of suppressing neointimal growth after vascular injury.

We performed whole-body irradiation and bone marrow transplantation experiments followed by carotid artery injury with ferric chloride in mice. Our results support the ability of bone marrow–derived cells to modulate neointimal growth after injury, which appears to be partly mediated by the expression of plasminogen activator inhibitor-1

Key Words: bone marrow–derived vascular progenitor cells • mouse model • plasminogen activator inhibitor • vascular injury

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