Abstract:
OBJECTIVES:In this study, our goal was to determine if human resistin plays a role in regulating the uptake of atherogenic low-density lipoproteins in human hepatocytes. BACKGROUND:Serum levels of resistin, an adipose tissue-derived adipokine, are increased in human obesity and are positively correlated with atherosclerotic cardiovascular diseases. However, the function of resistin in humans is enigmatic. METHODS:Human hepatocytes (HepG2 and primary) were treated (24 h) with the following: 1) purified human resistin at various concentrations, with and without lovastatin; and 2) obese human serum with elevated resistin levels or serum from which resistin was removed via antibody-immunoprecipitation. The effect of the treatments on cellular low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger ribonucleic acid and protein levels were determined by using real-time polymerase chain reaction and Western blotting, respectively. RESULTS:Resistin, at physiological levels observed in human obesity, down-regulated hepatocyte LDLR expression substantially (by 40%). A key mechanism by which human resistin inhibited LDLR levels was by increased cellular expression of the recently identified protease, PCSK9, which enhances intracellular LDLR lysosomal degradation. The quantitatively important role of human resistin in LDLR expression was demonstrated by antibody-immunoprecipitation removal of resistin in human serum, which decreased serum stimulation of hepatocyte LDLRs markedly (by 80%). Furthermore, resistin diminished statin-mediated up-regulation of the LDLR by 60%, implicating resistin in the relative ineffectiveness of statins in selective target populations. CONCLUSIONS:These results reveal for the first time that resistin is a highly attractive therapeutic target in ameliorating elevated serum low-density lipoprotein and, thereby, atherosclerotic cardiovascular diseases in obese humans.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Melone M,Wilsie L,Palyha O,Strack A,Rashid Sdoi
10.1016/j.jacc.2011.11.064subject
Has Abstractpub_date
2012-05-08 00:00:00pages
1697-705issue
19eissn
0735-1097issn
1558-3597pii
S0735-1097(12)00635-3journal_volume
59pub_type
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journal_title:Journal of the American College of Cardiology
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abstract::Left ventricular performance was evaluated noninvasively in 111 patients participating at one study center in the Norwegian Multicenter Study on Timolol After Myocardial Infarction. Systolic time intervals were measured in 55 patients treated with timolol and in 56 patients receiving placebo. Measurements were made be...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1987-01-01 00:00:00
abstract:OBJECTIVES:This study aimed to compare changes in coronary endothelial function, systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac) immunosuppression. BACKGROUND:Functional endothelial abnormalities and intimal thickening ar...
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更新日期:2006-04-18 00:00:00
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journal_title:Journal of the American College of Cardiology
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pub_type: 杂志文章,多中心研究
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更新日期:2018-11-13 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2000-11-01 00:00:00
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更新日期:2006-05-02 00:00:00
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更新日期:2006-04-04 00:00:00
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doi:10.1016/0735-1097(95)00342-8
更新日期:1995-11-15 00:00:00
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journal_title:Journal of the American College of Cardiology
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pub_type: 临床试验,杂志文章
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更新日期:2014-08-26 00:00:00
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更新日期:2011-02-08 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
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更新日期:2010-06-29 00:00:00
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更新日期:1995-11-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2002-10-02 00:00:00
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doi:10.1016/j.jacc.2012.12.018
更新日期:2013-03-05 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2005.02.087
更新日期:2005-08-02 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,meta分析
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更新日期:2001-01-01 00:00:00
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journal_title:Journal of the American College of Cardiology
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更新日期:2002-03-20 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(91)90813-o
更新日期:1991-09-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
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更新日期:2010-01-26 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(87)80402-3
更新日期:1987-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00