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    ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression (2004)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Schmeisser, Alexander
    Soehnlein, Oliver
    Illmer, Thomas
    Lorenz, Hanns-Martin
    Eskafi, Saeed
    Roerick, Olaf
    Gabler, Christoph
    Strasser, Ruth
    Daniel, Werner G
    Garlichs, Christoph D
    Quelle
    Biochemical and biophysical research communications; 325(2) — S. 532–540
    ISSN: 0006-291x
    Sprache
    Englisch
    Verweise
    Pubmed: 15530425
    Kontakt
    Institut für Veterinär-Biochemie

    Oertzenweg 19 b
    14163 Berlin
    +49 30 838 62225
    biochemie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Angiotensin converting enzyme (ACE) inhibitors significantly improve survival in patients with atherosclerosis. Although ACE inhibitors reduce local angiotensin II (AngII) formation, serine proteases form AngII to an enormous amount independently from ACE. Therefore, our study concentrates on the effect of the ACE-inhibitor ramiprilat on chemokine release, AngII receptor (ATR) expression, and NF-kappaB activity in monocytes stimulated with AngII.

    AngII-induced upregulation of IL-8 and MCP-1 protein and RNA in monocytes was inhibited by the AT1R-blocker losartan, but not by the AT2R-blocker PD 123.319. Ramiprilat dose-dependently suppressed AngII-induced upregulation of IL-8 and MCP-1. The suppressive effect of ramiprilat on AngII-induced chemokine production and release was in part caused by downregulation of NF-kappaB, but more by a selective and highly significant reduced expression of AT1 receptors as shown in monocytes and endothelial cells.

    In our study we demonstrated for the first time that ramiprilat reduced expression of AT1R in monocytes and endothelial cells. In addition, ramiprilat downregulated NF-kappaB activity and thereby reduced the AngII-induced release of IL-8 and MCP-1 in monocytes. This antiinflammatory effect, at least in part, may contribute to the clinical benefit of the ACE inhibitor in the treatment of coronary artery disease.