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Amlodipine suppresses PDGF-induced proliferation and ROS production via AMP-activated protein kinase signaling pathway in vascular smooth muscle cells
부산대학교
최정현, 최형철,김성애, 홍그루, 이명용
amlodipine is a selective L type calcium channel blocker which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that amlodipine may prevent a cell proliferation by the activation of AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of amlodipine besylate and amlodipine maleate. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Amlodipine increased the phosphorylation of AMPK both dose- and time-dependently and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Amlodipine also significantly decreased PDGF-induced VSMC proliferation by the cell cycle arrest and ROS production. Compound C and AMPK siRNA blocked amlodipine-induced inhibition of cell proliferation. These data suggest that amlodipine-induced AMPK activation might attenuate PDGF-induced VSMC proliferation through the inhibition of cell cycle progression.In conclusion, amlodipine inhibits PDGF-induced cell proliferation and ROS production through the phosphorylation of AMPK at Thr 172 residue.


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