Artemisinin attenuates platelet-derived growth factor BB-induced migration of vascular smooth muscle cells
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BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effectof AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferationof vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migrationwas measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by usingan EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measuredthrough H2DCF-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measuresof extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT (10 μM and 30 μM) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependentmanner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BBstimulated VSMC treated with AT (10 μM and 30 μM) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expressioncompared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulatedVSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.
Abstract
BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effectof AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferationof vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migrationwas measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by usingan EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measuredthrough H2DCF-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measuresof extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT (10 μM and 30 μM) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependentmanner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BBstimulated VSMC treated with AT (10 μM and 30 μM) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expressioncompared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulatedVSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.
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