This Article Full Text Full Text (PDF) All Versions of this Article: 106/1/36    most recent 01.CIR.0000020001.09990.90v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Damås, J. K. Articles by Aukrust, P. Search for Related Content PubMed PubMed Citation Articles by Damås, J. K. Articles by Aukrust, P. Pubmed/NCBI databases Substance via MeSH Related Collections Pathophysiology Growth factors/cytokines Coagulation Chronic ischemic heart disease Mechanism of atherosclerosis/growth factors

(Circulation. 2002;106:36.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Stromal Cell–Derived Factor-1 in Unstable Angina

Potential Antiinflammatory and Matrix-Stabilizing Effects

Jan K. Damås, MD, PhD; Torgun Wæhre, MD; Arne Yndestad, MSc; Thor Ueland, BS; Fredrik Müller, MD, PhD; Hans Geir Eiken, PhD; Are M. Holm, MD; Bente Halvorsen, PhD; Stig S. Frøland, MD, PhD; Lars Gullestad, MD, PhD; Pål Aukrust, MD, PhD

From the Research Institute for Internal Medicine (J.K.D., T.W., A.Y., T.U., F.M., H.G.E., A.M.H., B.H., S.S.F., P.A.), the Department of Cardiology (J.K.D., L.G.), MSD Cardiovascular Research Center (H.G.E.); Section of Endocrinology (T.U.), Section of Clinical Immunology and Infectious Diseases (A.M.H., S.S.F., P.A.), Rikshospitalet, Oslo, Norway.

Correspondence to Dr Pål Aukrust, Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet, N-0027 Oslo, Norway. E-mail pal.aukrust{at}rikshospitalet.no

Background— Chemokines play a pathogenic role in atherogenesis and plaque destabilization by activating and directing leukocytes into the atherosclerotic plaque. However, stromal cell–derived factor (SDF)-1 was recently found to have antiinflammatory effects, and we hypothesized that this chemokine could play a beneficial role in coronary artery disease.

Methods and Results— Plasma levels of SDF-1 were significantly decreased in patients with stable (n=30) and unstable angina (n=30) compared with healthy control subjects (n=20), particularly in those with unstable disease. By flow cytometry and RNase protection assay, we found decreased surface expression but increased gene expression of the SDF-1 receptor CXCR-4 in peripheral blood mononuclear cells (PBMC) from patients with stable angina and patients with unstable angina. In vitro, SDF-1 (500 ng/mL) reduced both unstimulated and endotoxin/mitogen-stimulated mRNA and protein levels of monocyte chemoattractant protein-1, interleukin-8, matrix metalloproteinase-9, and tissue factor while increasing tissue inhibitor of metalloproteinases-1 in PBMC from patients with unstable angina. The SDF-1–mediated suppression of monocyte chemoattractant protein-1 and interleukin-8 appears to involve cAMP/protein kinase A type I–dependent pathways. Finally, although SDF-1 suppressed the spontaneous release of these inflammatory mediators in unstable angina, enhancing effects were seen in unstimulated PBMC from healthy control subjects, possibly reflecting that PBMC in unstable angina are preactivated in vivo.

Conclusions— In contrast to several other chemokines, our findings suggest that SDF-1, at least in high concentrations, may mediate antiinflammatory and matrix-stabilizing effects in unstable angina. These effects may promote plaque stabilization, and therapeutic intervention that enhances SDF-1 activity could potentially be beneficial in acute coronary syndromes.

Key Words: angina • immunology • inflammation

This article has been cited by other articles:

				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]

				A.O. Kraaijeveld, S.C.A. de Jager, W.J. de Jager, B.J. Prakken, S.R. McColl, I. Haspels, H. Putter, T.J.C. van Berkel, L. Nagelkerken, J.W. Jukema, et al. CC Chemokine Ligand-5 (CCL5/RANTES) and CC Chemokine Ligand-18 (CCL18/PARC) Are Specific Markers of Refractory Unstable Angina Pectoris and Are Transiently Raised During Severe Ischemic Symptoms Circulation, October 23, 2007; 116(17): 1931 - 1941. [Abstract] [Full Text] [PDF]

				M Penicka, O Lang, P Widimsky, P Kobylka, T Kozak, T Vanek, J Dvorak, J Tintera, and J Bartunek One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction Heart, July 1, 2007; 93(7): 837 - 841. [Abstract] [Full Text] [PDF]

				A. Aicher, C. Heeschen, K.-i. Sasaki, C. Urbich, A. M. Zeiher, and S. Dimmeler Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells: A New Modality to Increase Efficacy of Cell Therapy in Chronic Hind Limb Ischemia Circulation, December 19, 2006; 114(25): 2823 - 2830. [Abstract] [Full Text] [PDF]

				P. Atluri, G. P. Liao, C. M. Panlilio, V. M. Hsu, M. J. Leskowitz, K. J. Morine, J. E. Cohen, M. F. Berry, E. E. Suarez, D. A. Murphy, et al. Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann. Thorac. Surg., May 1, 2006; 81(5): 1728 - 1736. [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]

				I. Elmadbouh, Y. Chen, L. Louedec, S. Silberman, B. Pouzet, O. Meilhac, and J.-B. Michel Mesothelial cell transplantation in the infarct scar induces neovascularization and improves heart function Cardiovasc Res, November 1, 2005; 68(2): 307 - 317. [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]

				C. Weber Platelets and Chemokines in Atherosclerosis: Partners in Crime Circ. Res., April 1, 2005; 96(6): 612 - 616. [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]

				W. Wojakowski, M. Tendera, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, R. Wyderka, A. Ochala, and M. Z. Ratajczak Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ Stem Cells, and Mononuclear Cells Expressing Early Cardiac, Muscle, and Endothelial Markers Into Peripheral Blood in Patients With Acute Myocardial Infarction Circulation, November 16, 2004; 110(20): 3213 - 3220. [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]

				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]

				A. M. Masci, M. Galgani, S. Cassano, S. De Simone, A. Gallo, V. De Rosa, S. Zappacosta, and L. Racioppi HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling J. Leukoc. Biol., December 1, 2003; 74(6): 1117 - 1124. [Abstract] [Full Text]

				A. Schober, S. Knarren, M. Lietz, E. A. Lin, and C. Weber Crucial Role of Stromal Cell-Derived Factor-1{alpha} in Neointima Formation After Vascular Injury in Apolipoprotein E-Deficient Mice Circulation, November 18, 2003; 108(20): 2491 - 2497. [Abstract] [Full Text] [PDF]

				C. B Jones, D. C Sane, and D. M Herrington Matrix metalloproteinases: A review of their structure and role in acute coronary syndrome Cardiovasc Res, October 1, 2003; 59(4): 812 - 823. [Abstract] [Full Text] [PDF]

				S. H. Chalasani, F. Baribaud, C. M. Coughlan, M. J. Sunshine, V. M. Y. Lee, R. W. Doms, D. R. Littman, and J. A. Raper The Chemokine Stromal Cell-Derived Factor-1 Promotes the Survival of Embryonic Retinal Ganglion Cells J. Neurosci., June 1, 2003; 23(11): 4601 - 4612. [Abstract] [Full Text] [PDF]

				T. Waehre, J. K. Damas, L. Gullestad, A. M. Holm, T. R. Pedersen, K. E. Arnesen, H. Torsvik, S. S. Froland, A. G. Semb, and P.a. Aukrust Hydroxymethylglutaryl coenzyme a reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1460 - 1467. [Abstract] [Full Text] [PDF]

				I. Risnes, T. Ueland, R. Lundblad, T. E. Mollnes, S. T. Baksaas, P. Aukrust, and J. L. Svennevig Changes in the cytokine network and complement parameters during open heart surgery Interactive CardioVascular and Thoracic Surgery, March 1, 2003; 2(1): 19 - 24. [Abstract] [Full Text] [PDF]