Artemisinin attenuates plantlet-derived growth factor BB-induced migration of vascular smooth muscle cells

Abstract

BACKGROUND/OBJECTIVESArtemisinin (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 effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB).MATERIALS/METHODSAortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through H2DCF-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR).RESULTSAT (10 µM and 30 µM) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT (10 µM and 30 µM) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC.CONCLUSIONSWe suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

Tetramethylpyrazine protects against high glucose-induced vascular smooth muscle cell injury through inhibiting the phosphorylation of JNK, p38MAPK, and ERK

“… 25 – 27 HG stimulation caused the up-regulation of p-ERK, p-JNK, and p-p38MAPK levels in VSMCs in the present study, which likely reflects increased intracellular ROS and the subsequent activation of downstream kinases. 28 – 30 Other reports found that TMP could accelerate the proliferation and migration of cerebral endothelial cells, and that its actions were strengthened when combined with soluble Fas ligand. TMP was also shown to reverse oxygen–glucose deprivation-induced Cx32 expression and apoptosis in cultured hippocampal neurons by regulating the ERK1/2 and p38MAPK pathways.…”

Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways

“…VSMC phenotypic switching have been associated with the MAPK pathway and Akt signaling (33,34). The maintenance of a contractile phenotype in VSMC was shown to be dependent on the Akt pathway, whereas activation of the ERK and p38 MAPK pathways induced proliferation (35 –37), thus indicating that the VSMC phenotype is determined by a balance between these pathways. MAPK is a group of protein kinases widely existing in cells with serine/threonine bi-phosphorylated protein kinase.…”

Zedoarondiol Inhibits Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells Proliferation via Regulating AMP-Activated Protein Kinase Signaling Pathway

“…Zedoarondiol is a sesquiterpenoid compound. Numerous studies evaluating sesquiterpenoids on VSMCs indicate that GADPH is widely used as a normalization control in western blotting and that GADPH expression appears unchanged with sesquiterpenoids treatment [52,53]. Based on these findings, we chose GADPH to normalize protein expression in our study.…”