Abstract：
:In mediating the transfer of cholesteryl esters (CE) from antiatherogenic high density lipoprotein (HDL) to proatherogenic apolipoprotein (apo)-B-containing lipoprotein particles (including very low density lipoprotein [VLDL], VLDL remnants, intermediate density lipoprotein [IDL], and low density lipoprotein [LDL]), the CE transfer protein (CETP) plays a critical role not only in the reverse cholesterol transport (RCT) pathway but also in the intravascular remodeling and recycling of HDL particles. Dyslipidemic states associated with premature atherosclerotic disease and high cardiovascular risk are characterized by a disequilibrium due to an excess of circulating concentrations of atherogenic lipoproteins relative to those of atheroprotective HDL, thereby favoring arterial cholesterol deposition and enhanced atherogenesis. In such states, CETP activity is elevated and contributes significantly to the cholesterol burden in atherogenic apoB-containing lipoproteins. In reducing the numbers of acceptor particles for HDL-derived CE, both statins (VLDL, VLDL remnants, IDL, and LDL) and fibrates (primarily VLDL and VLDL remnants) act to attenuate potentially proatherogenic CETP activity in dyslipidemic states; simultaneously, CE are preferentially retained in HDL and thereby contribute to elevation in HDL-cholesterol content. Mutations in the CETP gene associated with CETP deficiency are characterized by high HDL-cholesterol levels (>60 mg/dL) and reduced cardiovascular risk. Such findings are consistent with studies of pharmacologically mediated inhibition of CETP in the rabbit, which argue strongly in favor of CETP inhibition as a valid therapeutic approach to delay atherogenesis. Consequently, new organic inhibitors of CETP are under development and present a potent tool for elevation of HDL in dyslipidemias involving low HDL levels and premature coronary artery disease, such as the dyslipidemia of type II diabetes and the metabolic syndrome. The results of clinical trials to evaluate the impact of CETP inhibition on premature atherosclerosis are eagerly awaited.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Le Goff W,Guerin M,Chapman MJdoi
10.1016/j.pharmthera.2003.10.001subject
Has Abstractpub_date
2004-01-01 00:00:00pages
17-38issue
1eissn
0163-7258issn
1879-016Xpii
S0163725803001487journal_volume
101pub_type
杂志文章,评审abstract：:Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of ...
journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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更新日期：2016-12-01 00:00:00
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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abstract：:Despite difficulties in the interpretation of available data, certain general observations can be made on the epidemiology of poisioning. Childhood poisoning is usually accidental and tends to be associated with a low morbidity and mortality. In Western Europe and North America, it is most often due to household produ...
journal_title：Pharmacology & therapeutics
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abstract：:Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the ...
journal_title：Pharmacology & therapeutics
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