Document Detail


Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells.
MedLine Citation:
PMID:  21036148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism.
METHODS: Rat-derived VSMC cell line A10 treated with 50mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure.
RESULTS: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated.
CONCLUSION: Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1.
Authors:
Di-xian Luo; Cheng-lai Xia; Jun-mu Li; Yan Xiong; Hao-yu Yuan; Zhen-Wang Tang; Yixin Zeng; Duan-fang Liao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-29
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  403     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  52-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan, China. luodixian_2@163.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Caveolin 1 / metabolism*
Cells, Cultured
Cholesterol / metabolism*
Down-Regulation
Lipoproteins, LDL / pharmacology
Muscle, Smooth, Vascular / drug effects,  metabolism*
Pressure
Rats
Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors,  metabolism*
Chemical
Reg. No./Substance:
0/Caveolin 1; 0/Lipoproteins, LDL; 0/Sterol Regulatory Element Binding Protein 1; 0/oxidized low density lipoprotein; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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