Effects of rosuvastatin in homocysteine induced mouse vascular smooth muscle cell dedifferentiation and endoplasmic reticulum stress and its mechanisms.
10.12047/j.cjap.5489.2018.012
- Author:
Chang-Zuan ZHOU
1
;
Sun-Lei PAN
1
;
Hui LIN
1
;
Li-Ping MENG
1
;
Zheng JI
1
;
Ju-Fang CHI
1
;
Hang-Yuan GUO
1
Author Information
1. Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000.
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress;
homocysteine;
mouse;
phenotype dedifferentiation;
rosuvastatin;
vascular smooth muscle cell
- MeSH:
Actins;
metabolism;
Animals;
Calcium-Binding Proteins;
metabolism;
Cell Dedifferentiation;
drug effects;
Cells, Cultured;
Endoplasmic Reticulum Stress;
drug effects;
Heat-Shock Proteins;
metabolism;
Homocysteine;
Membrane Proteins;
metabolism;
Mice;
Microfilament Proteins;
metabolism;
Muscle, Smooth, Vascular;
cytology;
Myocytes, Smooth Muscle;
cytology;
drug effects;
Ribosomal Protein S6 Kinases, 70-kDa;
metabolism;
Rosuvastatin Calcium;
pharmacology;
TOR Serine-Threonine Kinases;
metabolism;
X-Box Binding Protein 1;
metabolism
- From:
Chinese Journal of Applied Physiology
2018;34(1):43-48
- CountryChina
- Language:Chinese
-
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.
