Crucial Role of Stromal Cell–Derived Factor-1α in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice
| Autor: | Michael Lietz, Elisa A. Lin, Sandra Knarren, Christian Weber, Andreas Schober |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Apolipoprotein E Neointima Pathology medicine.medical_specialty Stromal cell Apolipoprotein B Cell Separation Muscle Smooth Vascular Lesion Mice Apolipoproteins E Restenosis Physiology (medical) medicine Animals Antigens Ly Carotid Stenosis Cell Lineage Stromal cell-derived factor 1 Mice Knockout biology business.industry Stem Cells Angioplasty Antibodies Monoclonal Membrane Proteins medicine.disease Immunohistochemistry Chemokine CXCL12 Mice Inbred C57BL Carotid Arteries medicine.anatomical_structure Disease Progression biology.protein Female medicine.symptom Tunica Intima Cardiology and Cardiovascular Medicine business Chemokines CXC Stem Cell Transplantation Blood vessel |
| Zdroj: | Circulation. 108:2491-2497 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000099508.76665.9a |
| Popis: | Background—Recent evidence indicates that stromal cell–derived factor-1α (SDF-1α) 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-1α in neointimal formation after vascular injury.Methods and Results—SDF-1α 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-1α staining was mostly confined to smooth muscle cells (SMCs). Furthermore, SDF-1α plasma levels peaked 1 day after vascular injury. Treatment of apoE−/−mice after carotid injury with a neutralizing SDF-1α monoclonal antibody for 3 weeks reduced neointimal lesion area by 44% (n=5,P−/−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-1α. Systemic injection of isolated PBPCs after vascular injury demonstrated their recruitment to neointimal lesions, where they can adopt an SMC-like phenotype.Conclusions—SDF-1α 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-1α–dependent recruitment of circulating SMC progenitor cells. |
| Databáze: | OpenAIRE |
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