PMID- 29926658 OWN - NLM STAT- MEDLINE DCOM- 20190104 LR - 20231213 IS - 1000-6834 (Print) IS - 1000-6834 (Linking) VI - 34 IP - 1 DP - 2018 Jan 8 TI - [Effects of rosuvastatin in homocysteine induced mouse vascular smooth muscle cell dedifferentiation and endoplasmic reticulum stress and its mechanisms]. PG - 43-48 LID - 10.12047/j.cjap.5489.2018.012 [doi] AB - 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 mumol/L). Cytoskeleton remodeling, VSMCs phenotype markers (smooth muscle actin-alpha, 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 mumol/L) showed enhanced alpha-SMA and calponin expression (P<0.01), suppressed ERS mRNA levels (P<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 (P<0.01); while tunicamycin could reverse the effect of Rsv on Hcy treated cells. Furthermore, alleviated mTOR-P70S6K phosphorylation and ERS (P<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 (P<0.01). CONCLUSIONS: Rosuvastatin could inhibit Hcy induced VSMCs dedifferentiation via suppressing ERS, which might be regulated by mTOR-P70S6K signaling. FAU - Zhou, Chang-Zuan AU - Zhou CZ AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. AD - Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 32500, China. FAU - Pan, Sun-Lei AU - Pan SL AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. FAU - Lin, Hui AU - Lin H AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. FAU - Meng, Li-Ping AU - Meng LP AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. FAU - Ji, Zheng AU - Ji Z AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. FAU - Chi, Ju-Fang AU - Chi JF AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. FAU - Guo, Hang-Yuan AU - Guo HY AD - Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000. LA - chi PT - Journal Article PL - China TA - Zhongguo Ying Yong Sheng Li Xue Za Zhi JT - Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology JID - 9426407 RN - 0 (Actins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Heat-Shock Proteins) RN - 0 (Herpud1 protein, mouse) RN - 0 (Hspa5 protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (Microfilament Proteins) RN - 0 (X-Box Binding Protein 1) RN - 0 (Xbp1 protein, mouse) RN - 0 (alpha-smooth muscle actin, mouse) RN - 0LVT1QZ0BA (Homocysteine) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Actins/metabolism MH - Animals MH - Calcium-Binding Proteins/metabolism MH - Cell Dedifferentiation/*drug effects MH - Cells, Cultured MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/*drug effects MH - Heat-Shock Proteins/metabolism MH - Homocysteine MH - Membrane Proteins/metabolism MH - Mice MH - Microfilament Proteins/metabolism MH - Muscle, Smooth, Vascular/*cytology MH - Myocytes, Smooth Muscle/cytology/*drug effects MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Rosuvastatin Calcium/*pharmacology MH - TOR Serine-Threonine Kinases/metabolism MH - X-Box Binding Protein 1/metabolism MH - Calponins OTO - NOTNLM OT - endoplasmic reticulum stress OT - homocysteine OT - mouse OT - phenotype dedifferentiation OT - rosuvastatin OT - vascular smooth muscle cell EDAT- 2018/06/22 06:00 MHDA- 2019/01/05 06:00 CRDT- 2018/06/22 06:00 PHST- 2018/06/22 06:00 [entrez] PHST- 2018/06/22 06:00 [pubmed] PHST- 2019/01/05 06:00 [medline] AID - 10.12047/j.cjap.5489.2018.012 [doi] PST - ppublish SO - Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Jan 8;34(1):43-48. doi: 10.12047/j.cjap.5489.2018.012.