title: Stromal cell-derived factor-1alpha in unstable angina: potential antiinflammatory and matrix-stabilizing effects.
abstract: 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.
  
  
  RESULTS
  Plasma levels of SDF-1alpha 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-1alpha receptor CXCR-4 in peripheral blood mononuclear cells (PBMC) from patients with stable angina and patients with unstable angina. In vitro, SDF-1alpha (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-1alpha-mediated suppression of monocyte chemoattractant protein-1 and interleukin-8 appears to involve cAMP/protein kinase A type I-dependent pathways. Finally, although SDF-1alpha 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-1alpha, 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-1alpha activity could potentially be beneficial in acute coronary syndromes.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Fredrik
authors.initials: F
authors.lastname: Müller
authors.forename: Hans Geir
authors.initials: HG
authors.lastname: Eiken
authors.forename: Are M
authors.initials: AM
authors.lastname: Holm
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000789:Angina, Unstable / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D019715:Tissue Inhibitor of Metalloproteinase-1; D013925:Thromboplastin; D017868:Cyclic AMP-Dependent Protein Kinases; D020780:Matrix Metalloproteinase 9