Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000099508.76665.9A
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;108:2491.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Crucial Role of Stromal Cell–Derived Factor-1
in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice
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
(SDF-1) 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 in neointimal formation after vascular injury.
Methods and Results— SDF-1 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 staining was mostly confined to smooth muscle cells (SMCs). Furthermore, SDF-1 plasma levels peaked 1 day after vascular injury. Treatment of apoE-/- mice after carotid injury with a neutralizing SDF-1 monoclonal antibody for 3 weeks reduced neointimal lesion area by 44% (n=5, P<0.05) compared with isotype control. In SDF-1 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. 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 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–dependent recruitment of circulating SMC progenitor cells.
Key Words: restenosis • arteries • muscle, smooth • plaque
This article has been cited by other articles:
 |
|
 |
|
  R. A. Nemenoff, P. A. Simpson, S. B. Furgeson, N. Kaplan-Albuquerque, J. Crossno, P. J. Garl, J. Cooper, and M. C.M. Weiser-Evans Targeted Deletion of PTEN in Smooth Muscle Cells Results in Vascular Remodeling and Recruitment of Progenitor Cells Through Induction of Stromal Cell-Derived Factor-1{alpha} Circ. Res., May 9, 2008; 102(9): 1036 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, A. Zampetaki, A. Sidibe, U. Mayr, X. Yin, A. I. De Souza, Y.-L. Chung, B. Madhu, P. H. Quax, Y. Hu, et al. Proteomic and Metabolomic Analysis of Smooth Muscle Cells Derived From the Arterial Media and Adventitial Progenitors of Apolipoprotein E-Deficient Mice Circ. Res., May 9, 2008; 102(9): 1046 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tanaka, M. Sata, T. Natori, J.-r. Kim-Kaneyama, K. Nose, M. Shibanuma, Y. Hirata, and R. Nagai Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice FASEB J, February 1, 2008; 22(2): 428 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zernecke, I. Bot, Y. Djalali-Talab, E. Shagdarsuren, K. Bidzhekov, S. Meiler, R. Krohn, A. Schober, M. Sperandio, O. Soehnlein, et al. Protective Role of CXC Receptor 4/CXC Ligand 12 Unveils the Importance of Neutrophils in Atherosclerosis Circ. Res., February 1, 2008; 102(2): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Stellos, H. Langer, K. Daub, T. Schoenberger, A. Gauss, T. Geisler, B. Bigalke, I. Mueller, M. Schumm, I. Schaefer, et al. Platelet-Derived Stromal Cell Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+ Cells to Endothelial Progenitor Cells Circulation, January 15, 2008; 117(2): 206 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Karshovska, A. Zernecke, G. Sevilmis, A. Millet, M. Hristov, C. D. Cohen, H. Schmid, F. Krotz, H.-Y. Sohn, V. Klauss, et al. Expression of HIF-1{alpha} in Injured Arteries Controls SDF-1{alpha} Mediated Neointima Formation in Apolipoprotein E Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2540 - 2547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Krohn, U. Raffetseder, I. Bot, A. Zernecke, E. Shagdarsuren, E. A. Liehn, P. J. van Santbrink, P. J. Nelson, E. A. Biessen, P. R. Mertens, et al. Y-Box Binding Protein-1 Controls CC Chemokine Ligand-5 (CCL5) Expression in Smooth Muscle Cells and Contributes to Neointima Formation in Atherosclerosis-Prone Mice Circulation, October 16, 2007; 116(16): 1812 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morimoto, M. Takahashi, Y. Shiba, A. Izawa, H. Ise, M. Hongo, K. Hatake, K. Motoyoshi, and U. Ikeda Bone Marrow-Derived CXCR4+ Cells Mobilized by Macrophage Colony-Stimulating Factor Participate in the Reduction of Infarct Area and Improvement of Cardiac Remodeling after Myocardial Infarction in Mice Am. J. Pathol., September 1, 2007; 171(3): 755 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Massberg, I. Konrad, K. Schurzinger, M. Lorenz, S. Schneider, D. Zohlnhoefer, K. Hoppe, M. Schiemann, E. Kennerknecht, S. Sauer, et al. Platelets secrete stromal cell-derived factor 1{alpha} and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo J. Exp. Med., May 15, 2006; 203(5): 1221 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-N. Zhang, D. W. Wilson, V. da Cunha, M. E. Sullivan, R. Vergona, J. C. Rutledge, and Y.-X. Wang Endothelial NO Synthase Deficiency Promotes Smooth Muscle Progenitor Cells in Association With Upregulation of Stromal Cell-Derived Factor-1{alpha} in a Mouse Model of Carotid Artery Ligation Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 765 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Carr, B. W. Howard, H. T. Yang, E. Eby-Wilkens, P. Loos, A. Varbanov, A. Qu, J. P. DeMuth, M. G. Davis, A. Proia, et al. Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: Support for an endothelium-dependent mechanism Cardiovasc Res, March 1, 2006; 69(4): 925 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kodali, M. Hajjou, A. B. Berman, M. B. Bansal, S. Zhang, J. J. Pan, and A. D. Schecter Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells Cardiovasc Res, February 15, 2006; 69(3): 706 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Quehenberger Thematic Review Series: The Immune System and Atherogenesis. Molecular mechanisms regulating monocyte recruitment in atherosclerosis J. Lipid Res., August 1, 2005; 46(8): 1582 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tanaka, M. Sata, D. Fukuda, Y. Suematsu, N. Motomura, S. Takamoto, Y. Hirata, and R. Nagai Age-Associated Aortic Stenosis in Apolipoprotein E-Deficient Mice J. Am. Coll. Cardiol., July 5, 2005; 46(1): 134 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. W. Raines and N. Ferri Thematic Review Series: The Immune System and Atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular disease J. Lipid Res., June 1, 2005; 46(6): 1081 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zernecke, A. Schober, I. Bot, P. von Hundelshausen, E. A. Liehn, B. Mopps, M. Mericskay, P. Gierschik, E. A. Biessen, and C. Weber SDF-1{alpha}/CXCR4 Axis Is Instrumental in Neointimal Hyperplasia and Recruitment of Smooth Muscle Progenitor Cells Circ. Res., April 15, 2005; 96(7): 784 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weber Platelets and Chemokines in Atherosclerosis: Partners in Crime Circ. Res., April 1, 2005; 96(6): 612 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Spencer, S. L. Hacker, E. C. Davis, R. P. Mecham, R. H. Knutsen, D. Y. Li, R. D. Gerard, J. A. Richardson, E. N. Olson, and H. Yanagisawa Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration PNAS, February 22, 2005; 102(8): 2946 - 2951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schober, A. Zernecke, E. A. Liehn, P. von Hundelshausen, S. Knarren, W. A. Kuziel, and C. Weber Crucial Role of the CCL2/CCR2 Axis in Neointimal Hyperplasia After Arterial Injury in Hyperlipidemic Mice Involves Early Monocyte Recruitment and CCL2 Presentation on Platelets Circ. Res., November 26, 2004; 95(11): 1125 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Abbott, Y. Huang, D. Liu, R. Hickey, D. S. Krause, and F. J. Giordano Stromal Cell-Derived Factor-1{alpha} Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury Circulation, November 23, 2004; 110(21): 3300 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Straino, A. Germani, A. Di Carlo, D. Porcelli, R. De Mori, A. Mangoni, M. Napolitano, F. Martelli, P. Biglioli, and M. C. Capogrossi Enhanced Arteriogenesis and Wound Repair in Dystrophin-Deficient mdx Mice Circulation, November 23, 2004; 110(21): 3341 - 3348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weber, A. Schober, and A. Zernecke Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1997 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. F. Charo and M. B. Taubman Chemokines in the Pathogenesis of Vascular Disease Circ. Res., October 29, 2004; 95(9): 858 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Liehn, A. Schober, and C. Weber Blockade of Keratinocyte-Derived Chemokine Inhibits Endothelial Recovery and Enhances Plaque Formation After Arterial Injury in ApoE-Deficient Mice Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1891 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Hiasa, M. Ishibashi, K. Ohtani, S. Inoue, Q. Zhao, S. Kitamoto, M. Sata, T. Ichiki, A. Takeshita, and K. Egashira Gene Transfer of Stromal Cell-Derived Factor-1{alpha} Enhances Ischemic Vasculogenesis and Angiogenesis via Vascular Endothelial Growth Factor/Endothelial Nitric Oxide Synthase-Related Pathway: Next-Generation Chemokine Therapy for Therapeutic Neovascularization Circulation, May 25, 2004; 109(20): 2454 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Zeiffer, A. Schober, M. Lietz, E. A. Liehn, W. Erl, N. Emans, Z.-q. Yan, and C. Weber Neointimal Smooth Muscle Cells Display a Proinflammatory Phenotype Resulting in Increased Leukocyte Recruitment Mediated by P-Selectin and Chemokines Circ. Res., April 2, 2004; 94(6): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Werner and G. Nickenig From Fat Fighter to Risk Factor: The Zigzag Trek of Leptin Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 7 - 9. [Full Text] [PDF]
|
|