Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration
Joint Authors
Durst, Renate
Rottbauer, Wolfgang
Walcher, Thomas
Bernhardt, Peter
Bach, Helga
Walcher, Daniel
Vasic, Dusica
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-12-05
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Aims.
Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis.
Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation.
Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes.
Methods and results.
Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7).
Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7).
The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays.
Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC).
Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration.
Conclusion.
Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes.
Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.
American Psychological Association (APA)
Walcher, Thomas& Bernhardt, Peter& Vasic, Dusica& Bach, Helga& Durst, Renate& Rottbauer, Wolfgang…[et al.]. 2010. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration. Mediators of Inflammation،Vol. 2010, no. 2010, pp.1-8.
https://search.emarefa.net/detail/BIM-495847
Modern Language Association (MLA)
Walcher, Thomas…[et al.]. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration. Mediators of Inflammation No. 2010 (2010), pp.1-8.
https://search.emarefa.net/detail/BIM-495847
American Medical Association (AMA)
Walcher, Thomas& Bernhardt, Peter& Vasic, Dusica& Bach, Helga& Durst, Renate& Rottbauer, Wolfgang…[et al.]. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration. Mediators of Inflammation. 2010. Vol. 2010, no. 2010, pp.1-8.
https://search.emarefa.net/detail/BIM-495847
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-495847