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CJAP ›› 2018, Vol. 34 ›› Issue (1): 43-48.doi: 10.12047/j.cjap.5489.2018.012

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Effects of rosuvastatin in homocysteine induced mouse vascular smooth muscle cell dedifferentiation and endoplasmic reticulum stress and its mechanisms

ZHOU Chang-zuan1,2, PAN Sun-lei1, LIN Hui1, MENG Li-ping1, JI Zheng1, CHI Ju-fang1, GUO Hang-yuan1   

  1. 1. Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000;
    2. Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 32500, China
  • Received:2016-09-09 Revised:2017-06-27 Online:2018-01-28 Published:2018-06-19
  • Supported by:
    浙江省省部共建重点项目(WKJ-ZJ-1729)

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 (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).Conclusion: Rosuvastatin could inhibit Hcy induced VSMCs dedifferentiation via suppressing ERS, which might be regulated by mTOR-P70S6K signaling.

Key words: phenotype dedifferentiation, vascular smooth muscle cell, rosuvastatin, endoplasmic reticulum stress, homocysteine, mouse

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