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• W2139275890 abstract "Migration of CD4-positive lymphocytes into the vessel wall represents an important step in early atherogenesis. Telmisartan is an angiotensin type 1 receptor (AT1R) blocker with peroxisome proliferator-activated receptor (PPAR)-γ–activating properties. The present study examined the effect of telmisartan on CD4-positive cell migration and the role of PPARγ in this context. CD4-positive lymphocytes express both the AT1R and PPARγ. Stimulation of CD4-positive lymphocytes with stromal cell-derived factor (SDF)-1 leads to a 4.1±3.1-fold increase in cell migration. Pretreatment of cells with telmisartan reduces this effect in a concentration-dependent manner to a maximal 1.6±0.7-fold induction at 10 μmol/L of telmisartan ( P <0.01 compared with SDF-1–treated cells; n=22). Three different PPARγ activators, rosiglitazone, pioglitazone, and GW1929, had similar effects, whereas eprosartan, a non-PPARγ–activating AT1R blocker, did not affect chemokine-induced lymphocyte migration. Telmisartan’s effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced phosphatidylinositol 3-kinase activity. Downstream, telmisartan inhibited F-actin formation, as well as intercellular adhesion molecule-3 translocation. Transfection of CD4-positive lymphocytes with PPARγ small interfering RNA abolished telmisartan’s effect on migration, whereas blockade of the AT1R had no such effect. Telmisartan inhibits chemokine-induced CD4-positive cell migration independent of the AT1R via PPARγ. These data provide a novel mechanism to explain how telmisartan modulates lymphocyte activation by its PPARγ-activating properties." @default.
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• W2139275890 date "2008-02-01" @default.
• W2139275890 modified "2023-10-01" @default.
• W2139275890 title "Telmisartan Inhibits CD4-Positive Lymphocyte Migration Independent of the Angiotensin Type 1 Receptor via Peroxisome Proliferator-Activated Receptor-γ" @default.
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• W2139275890 doi "https://doi.org/10.1161/hypertensionaha.107.099028" @default.
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