Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade.

Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade. Int Heart J. 2018 Apr 20;: Authors: Kayamori H, Shimizu I, Yoshida Y, Hayashi Y, Suda M, Ikegami R, Katsuumi G, Wakasugi T, Minamino T Abstract Vascular cells have a finite lifespan and eventually enter irreversible growth arrest called cellular senescence. We have previously suggested that vascular cell senescence contributes to the pathogenesis of human atherosclerosis. Amlodipine is a mixture of two enantiomers, one of which (S- enantiomer) has L-type channel blocking activity, while the other (R+ enantiomer) shows ~1000-fold weaker channel blocking activity than S- enantiomer and has other unknown effects. It has been reported that amlodipine inhibits the progression of atherosclerosis in humans, but the molecular mechanism of this beneficial effect remains unknown. Apolipoprotein E-deficient mice on a high-fat diet were treated with amlodipine, its R+ enantiomer or vehicle for eight weeks. Compared with vehicle treatment, both amlodipine and the R+ enantiomer significantly reduced the number of senescent vascular cells and inhibited plaque formation to a similar extent. Expression of the pro-inflammatory molecule interleukin-1β was markedly upregulated in vehicle-treated mice, but was inhibited to a similar extent by treatment with amlodipine or the R+ enantiomer. Likewise, activation of...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research