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Circulation. 2003;108:2491-2497
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000099508.76665.9A
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(Circulation. 2003;108:2491.)
© 2003 American Heart Association, Inc.


Basic Science Reports

Crucial Role of Stromal Cell–Derived Factor-1{alpha} in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice

Andreas Schober, MD; Sandra Knarren, BS; Michael Lietz, PhD; Elisa A. Lin, MD; Christian Weber, MD

From the Department of Molecular Cardiovascular Research (A.S., S.K., M.L., E.A.L., C.W.) and Department of Cardiology (A.S., C.W.), University Hospital, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.

Correspondence to Dr Christian Weber, Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. E-mail cweber{at}ukaachen.de

Received August 27, 2003; revision received September 19, 2003; accepted September 22, 2003.

Background— Recent evidence indicates that stromal cell–derived factor-1{alpha} (SDF-1{alpha}) is expressed in human atherosclerotic plaques, whereas high plasma levels are clinically associated with stable coronary artery disease. Herein, we investigate the involvement of SDF-1{alpha} in neointimal formation after vascular injury.

Methods and Results— SDF-1{alpha} was detected by immunohistochemistry in carotid arteries of apolipoprotein E–deficient (apoE-/-) mice at various stages of neointima formation after wire-induced injury. Double immunofluorescence revealed that SDF-1{alpha} staining was mostly confined to smooth muscle cells (SMCs). Furthermore, SDF-1{alpha} plasma levels peaked 1 day after vascular injury. Treatment of apoE-/- mice after carotid injury with a neutralizing SDF-1{alpha} monoclonal antibody for 3 weeks reduced neointimal lesion area by 44% (n=5, P<0.05) compared with isotype control. In SDF-1{alpha} antibody–treated apoE-/- mice, neointimal SMC content was decreased (21.7±2% versus 39.4±4%, n=5, P=0.005), whereas the relative content of neointimal macrophages remained unchanged. As shown by flow cytometry, carotid injury resulted in a marked expansion of circulating Sca-1+lineage- progenitor cells (PBPCs) in the peripheral blood of apoE-/- mice after 1 day, which was mediated by SDF-1{alpha}. Systemic injection of isolated PBPCs after vascular injury demonstrated their recruitment to neointimal lesions, where they can adopt an SMC-like phenotype.

Conclusions— SDF-1{alpha} plays an instrumental role in neointimal formation after vascular injury in apoE-/- mice by regulating neointimal SMC content. This contribution appears to be attributable to SDF-1{alpha}–dependent recruitment of circulating SMC progenitor cells.


Key Words: restenosis • arteries • muscle, smooth • plaque




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