| Involvement of angiotensin II in intestinal cholesterol absorption. | |
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MedLine Citation:
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PMID: 20005956 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Niemann-Pick C1-like 1 (NPC1L1) protein is identified as a key molecule of cholesterol absorption into the intestine. Although there is a controversy about the association between sitosterol levels and cardiovascular disease (CVD), cholesterol absorption may contribute to the increased risk for CVD because increased levels of sitosterol, a marker of cholesterol absorption, are associated with future cardiovascular events in high-risk patients. However, which anthropometric and metabolic variables could regulate serum levels of sitosterol in humans and whether serum sitosterol levels might reflect transport function of NPC1L1 are largely unknown. In this study, we first investigated the independent determinants of serum sitosterol levels in apparently healthy patients not taking lipid-lowering agents. We next examined the effects of angiotensin II on NPC1L1 gene and protein expression in differentiated Caco-2 cells. Seventy apparently health patients not taking lipid-lowering agents (28 men and 42 women, mean age 73.7+/-10.1 years old) underwent a complete history and physical examination, determination of blood chemistries, including serum levels of sitosterol. Univariate regression analysis showed that serum levels of sitosterol were associated with low-density-lipoprotein (LDL)-cholesterol (r=0.284, p=0.021) and use of the renin-angiotensin system (RAS) inhibitors (r=-0.289, p=0.018). By the use of multiple stepwise regression analyses, use of RAS inhibitors (p=0.025) was remained significant independently. Further, angiotensin II was found to up-regulate NPC1L1 mRNA and protein levels in Caco-2 cells, which were completely blocked by an angiotensin II type 1 receptor blocker or an anti-oxidant, N-acetylcysteine. The present study suggests the possible involvement of RAS in NPC1L1 expression in vitro and cholesterol absorption in humans. |
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Authors:
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Kazuo Nakamura; Takanori Matsui; Hisashi Adachi; Sho-Ichi Yamagishi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-24 |
Journal Detail:
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Title: Pharmacological research : the official journal of the Italian Pharmacological Society Volume: 61 ISSN: 1096-1186 ISO Abbreviation: Pharmacol. Res. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-02 Completed Date: 2010-07-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8907422 Medline TA: Pharmacol Res Country: England |
Other Details:
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Languages: eng Pagination: 460-5 Citation Subset: IM |
Copyright Information:
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(c) 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Nakamura Clinic, Kita-Kyushu, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Alkaline Phosphatase / metabolism Angiotensin II / physiology* Antilipemic Agents / pharmacology Blotting, Western Caco-2 Cells Cholesterol / metabolism* Female Gene Expression / drug effects Humans Intestinal Absorption / physiology* Male Membrane Proteins / genetics Middle Aged RNA, Messenger / biosynthesis, genetics Regression Analysis Renin-Angiotensin System / drug effects Reverse Transcriptase Polymerase Chain Reaction Sitosterols / blood |
| Chemical | |
Reg. No./Substance:
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0/Antilipemic Agents; 0/Membrane Proteins; 0/NPC1L1 protein, human; 0/RNA, Messenger; 0/Sitosterols; 11128-99-7/Angiotensin II; 57-88-5/Cholesterol; 5779-62-4/sitosterol; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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