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Ivabradine reduces chemokine-induced CD4-positive lymphocyte migration. | LitMetric

Ivabradine reduces chemokine-induced CD4-positive lymphocyte migration.

Mediators Inflamm

Department of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Straresse, 89081 Ulm, Germany.

Published: April 2011

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003966PMC
http://dx.doi.org/10.1155/2010/751313DOI Listing

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