scholarly journals Inhibitory Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells (VSMCs) Through Suppression of the ERK1/2 Pathway

2010 ◽  
Vol 17 (10) ◽  
pp. 1009-1018 ◽  
Author(s):  
A Rum Yoo ◽  
Seong-Ho Koh ◽  
Goang Won Cho ◽  
Seung H Kim
2003 ◽  
Vol 44 (6) ◽  
pp. 963-978 ◽  
Author(s):  
Toshiaki Nakajima ◽  
Ji Ma ◽  
Haruko Iida ◽  
Kuniaki Iwasawa ◽  
Taisuke Jo ◽  
...  

2003 ◽  
Vol 178 (2) ◽  
pp. 319-329 ◽  
Author(s):  
K Takahashi ◽  
M Ohmichi ◽  
M Yoshida ◽  
K Hisamoto ◽  
S Mabuchi ◽  
...  

The proliferation of vascular smooth muscle cells (VSMC) is a crucial pathophysiological process in the development of atherosclerosis. Although estrogen is known to inhibit the proliferation of VSMC, the mechanism responsible for this effect remains to be elucidated. In addition, the effect of raloxifene on VSMC remains unknown. We have shown here that 17beta-estradiol (E(2)) and raloxifene significantly inhibited the platelet-derived growth factor (PDGF)-stimulated proliferation of cultured human VSMC. Flow cytometry demonstrated that PDGF-stimulated S-phase progression of the cell cycle in VSMC was also suppressed by E(2) or raloxifene. We found that PDGF-induced phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by E(2) and raloxifene. These effects were associated with a decrease in cyclin D1 expression, without a change in cyclin-dependent kinase 4 or cyclin-dependent kinase inhibitor, p27(kip1) expression. ICI 182,780 abolished the inhibitory effects of E(2) and raloxifene on PDGF-induced pRb phosphorylation. Next, we examined which estrogen receptor (ER) is necessary for these effects of E(2) and raloxifene. Since VSMC express both ERalpha and ERbeta, A10, a rat aortic smooth muscle cell line that expresses ERbeta but not ERalpha, was used. The dose-dependent stimulation of A10 cell proliferation by PDGF was not inhibited by E(2) or raloxifene in contrast to the results obtained in VSMC. Moreover, E(2) and raloxifene significantly inhibited the PDGF-induced cyclin D1 promoter activity in A10 cells transfected with cDNA for ERalpha but not in the parental cells. These results suggested that E(2) and raloxifene exert an antiproliferative effect in VSMC treated with PDGF, at least in part through inhibition of pRb phosphorylation, and that the inhibitory effects of E(2) and raloxifene may be mainly mediated by ERalpha.


2009 ◽  
Vol 60-61 ◽  
pp. 125-129
Author(s):  
Su Su Zhao ◽  
Qin Lu ◽  
Dong Sheng Zhang

Proliferation and migration of vascular smooth muscle cells(VSMCs) into the sub-intimal space play an important role in intimal thickening in atherosclerosis and in-stent restenosis. Arsenic compounds are natural substances that have been used in the treatment of patients with acute promyelocytic leukemia (APL).And Arsenic trioxide (As2O3) is known to be a potent inhibitor of cell proliferation.The aim of this study was to prepare arsenic trioxide (As2O3) -loaded PLGA nanoparticles(As2O3-PLGA-NP) and investigate its general properties, preservation of As2O3 bioactivity and their inhibitory effects on Rabbit Vascular Smooth Muscle Cells(RVSMCs) in vitro. With PLGA as carrier,As2O3 drug delivery nanoparticles were prepared by w /o /w double-emulsion evaporation technique,and their inhibitory effects on Rabbit Vascular Smooth Muscle Cells(VSMCs) in vitro was investigated.The results of the experiment show the self-prepared As2O3-PLGA-NP were approximately spherical,with the mean diameter of 90±25.03 nm, and the average drug loading was 1.72% .The As2O3-PLGA-NP has drug sustained-release character and can prolong the phase of the inhibitory effect of As2O3 against RVSMCs.The As2O3-PLGA-NP do not reduce the biological activity of As2O3.


2015 ◽  
Vol 13 (1) ◽  
pp. 426-432 ◽  
Author(s):  
JUN-HUI SONG ◽  
GI HEE JEONG ◽  
SUNG LYEA PARK ◽  
SE YEON WON ◽  
NAM SOO PAEK ◽  
...  

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