| Altered Metabolism of Low-density Lipoprotein and Very Low-density Lipoprotein Remnant in Autosomal Recessive Hypercholesterolemia: Results from Stable Isotope Kinetic Study in vivo. | |
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MedLine Citation:
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PMID: 22157599 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: -Autosomal recessive hypercholesterolemia (ARH) exhibits different responsiveness to statins compared with that in homozygous familial hypercholesterolemia (FH). However, few data exist regarding lipoprotein metabolism of ARH. Therefore, we aimed to clarify lipoprotein metabolism, especially, the remnant lipoprotein fractions of ARH before and after statin therapy. METHODS AND RESULTS: -We performed a lipoprotein kinetic study in an ARH patient and seven normal controls using stable isotope methodology. (10mg/kg of [(2)H(3)]-leucine). These studies were performed at baseline and after the 20mg daily of atorvastatin. Tracer/tracee ratio of apolipoprotein B (apoB) was determined by gas chromatography/mass spectrometry and fractional catabolic rates (FCR) were determined by multi-compartmental modeling including remnant lipoprotein fractions. FCR of LDL apoB of ARH was significantly lower than those of controls (0.109 vs. 0.450±0.122 pools/day). In contrast, the direct removals of VLDL remnant were significantly greater in ARH than those in controls (47.5 vs. 2±2 %). Interestingly, FCR of LDL apoB in ARH dramatically increased to 0.464 pools/day accompanying reduction of LDL-C levels from 8.63 to 4.22 mmol/L after treatment with atorvastatin of 20 mg/day for three months. CONCLUSIONS: -These results demonstrate that ARH exhibits decreased LDL clearance associated with decreased FCR of LDL apoB, and increased clearance for VLDL remnant. We suggest that increased clearance of remnant lipoprotein fractions could contribute to the great responsiveness to statins, providing new insights into the lipoprotein metabolism of ARH and the novel pharmacological target for LDLRAP1. |
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Authors:
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Hayato Tada; Masa-Aki Kawashiri; Katsunori Ikewaki; Yoshio Terao; Tohru Noguchi; Chiaki Nakanishi; Masayuki Tsuchida; Mutsuko Takata; Kenji Miwa; Tetsuo Konno; Kenshi Hayashi; Atsushi Nohara; Akihiro Inazu; Junji Kobayashi; Hiroshi Mabuchi; Masakazu Yamagishi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-9 |
Journal Detail:
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Title: Circulation. Cardiovascular genetics Volume: - ISSN: 1942-3268 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101489144 Medline TA: Circ Cardiovasc Genet Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Kanazawa University Graduate School of Medicine, Kanazawa, Japan; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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