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


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(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 sufficient to reduce luminal stenosis.


CONCLUSIONS
PAI-1 from BM-derived cells appears capable of suppressing neointimal growth after vascular injury.
Schäfer
Katrin
K
Department of Cardiology and Pulmonology, Georg August University School of Medicine, Goettingen, Germany. kschaefer@med.uni-goettingen.de
Schroeter
Marco R
MR
Dellas
Claudia
C
Puls
Miriam
M
Nitsche
Mirko
M
Weiss
Elisabeth
E
Hasenfuss
Gerd
G
Konstantinides
Stavros V
SV
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002339:Carotid Arteries / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016893:Carotid Stenosis / Q000473:pathology; D002454:Cell Differentiation; D002712:Chlorides; D004247:DNA / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000503:physiopathology; D013997:Time Factors; D017539:Tunica Intima / Q000254:growth & development* / Q000473:pathology; D014998:Y Chromosome
D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; D004247:DNA; C024555:ferric chloride