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-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.
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-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: Hongkuan Fan; Donald Wong; Sarah H Ashton; Keith T Borg; Perry V Halushka; James A Cook Journal: Inflammation Date: 2012-02 Impact factor: 4.092
Authors: Ilze Bot; Isabelle T M N Daissormont; Alma Zernecke; Gijs H M van Puijvelde; Birgit Kramp; Saskia C A de Jager; Judith C Sluimer; Marco Manca; Veronica Hérias; Marijke M Westra; Martine Bot; Peter J van Santbrink; Theo J C van Berkel; Lishan Su; Mona Skjelland; Lars Gullestad; Johan Kuiper; Bente Halvorsen; Paul Aukrust; Rory R Koenen; Christian Weber; Erik A L Biessen Journal: J Mol Cell Cardiol Date: 2014-05-08 Impact factor: 5.000
Authors: C G Egan; R Lavery; F Caporali; C Fondelli; F Laghi-Pasini; F Dotta; V Sorrentino Journal: Diabetologia Date: 2008-02-20 Impact factor: 10.122