ABSTRACT
OBJECTIVE@#To investigate the effect of rosuvastatin on homocysteine (Hcy) induced mousevascular smooth muscle cells(VSMCs) dedifferentiation and endoplasmic reticulum stress(ERS).@*METHODS@#VSMCs were co-cultured with Hcy and different concentration of rosuvastatin (0.1, 1.0 and 10 μmol/L). Cytoskeleton remodeling, VSMCs phenotype markers (smooth muscle actin-α, calponin and osteopontin) and ERS marker mRNAs (Herpud1, XBP1s and GRP78) were detected at predicted time. Tunicamycin was used to induce, respectively 4-phenylbutyrate(4-PBA) inhibition, ERS in VSMCs and cellular migration, proliferation and expression of phenotype proteins were analyzed. Mammalian target of rapamycin(mTOR)-P70S6 kinase (P70S6K) signaling agonist phosphatidic acid and inhibitor rapamycin were used in Rsv treated VSMCs. And then mTOR signaling and ERS associated mRNAs were detected.@*RESULTS@#Compared with Hcy group, Hcy+ Rsv group (1.0 and 10 μmol/L) showed enhanced α-SMA and calponin expression (<0.01), suppressed ERS mRNA levels (<0.01) and promoted polarity of cytoskeleton. Compared with Hcy group, Hcy+Rsv group and Hcy+4-PBA group showed suppressed proliferation, migration and enhanced contractile protein expression (<0.01); while tunicamycin could reverse the effect of Rsv on Hcy treated cells. Furthermore, alleviated mTOR-P70S6K phosphorylation and ERS (<0.01)were observed in Hcy+Rsv group and Hcy+rapamycin group, compared with Hcy group; while phosphatidic acid inhibited the effect of Rsv on mTOR signaling activation and ERS mRNA levels (<0.01).@*CONCLUSIONS@#Rosuvastatin could inhibit Hcy induced VSMCs dedifferentiation suppressing ERS, which might be regulated by mTOR-P70S6K signaling.
Subject(s)
Animals , Mice , Actins , Metabolism , Calcium-Binding Proteins , Metabolism , Cell Dedifferentiation , Cells, Cultured , Endoplasmic Reticulum Stress , Heat-Shock Proteins , Metabolism , Homocysteine , Membrane Proteins , Metabolism , Microfilament Proteins , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Cell Biology , Ribosomal Protein S6 Kinases, 70-kDa , Metabolism , Rosuvastatin Calcium , Pharmacology , TOR Serine-Threonine Kinases , Metabolism , X-Box Binding Protein 1 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the active ingredients in the Chinese yellow wine could inhibit the proliferation and migration of rat vascular smooth muscle cells induced by homocysteine (Hcy).</p><p><b>METHODS</b>The primary culture and identification of rat vascular smooth muscle cells (VSMCs) was conducted, and the VSMCs in passage 4-7 were used in the following experiments. The VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, Hcy + Chinese yellow wine and were given the corresponding treatment. The proliferation of VSMCs was determined by MTT. Transwell chambers and would healing were employed to test the migratory ability of VSMCs. Wester blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP-2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs of each group.</p><p><b>RESULTS</b>Compared with control group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly increased in the VSMCs of Hcy group (P < 0.01). Compared with Hcy group, the proliferation, migration and the expression and activity of MMP-2/9 of VSMCs were significantly decreases in the VSMCs of polypeptides group, polyphenols group and Chinese yellow wine group. However, the expression of TIMP-2 among each group had no significant difference.</p><p><b>CONCLUSION</b>Polypeptides and polyphenols in the Chinese yellow wine could inhibit the proliferation and migration of VSMCs induced by Hcy.</p>