Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a)
Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). The kinetics of apo(a) and apoB-100 in plasma Lp(a) were asse...
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| Vydané v: | Metabolism, clinical and experimental Ročník 65; číslo 4; s. 381 - 390 |
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| Hlavní autori: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
Elsevier Inc
01.04.2016
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| ISSN: | 0026-0495, 1532-8600, 1532-8600 |
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| Abstract | Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).
The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9–124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-2H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.
Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day−1 was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day−1 (P=0.03).
Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. |
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| AbstractList | Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).
The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.
Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).
Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. Objectives: Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). Materials and Methods: The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7 nmol/L]. All subjects received a primed constant infusion of [5,5,5- super(2)H sub(3)] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Results: Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P = 0.04). The median Lp(a) apo(a) production rate at 0.248 nmol/kg . day super(- 1) was significantly lower than that of Lp(a) apoB-100 at 0.514 nmol/kg . day super(- 1) (P = 0.03). Conclusion: Our data indicate that apo(a) has a plasma residence time (11 days) that is more than twice as long as that of apoB-100 (4 days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).OBJECTIVESLipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.MATERIALS AND METHODSThe kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).RESULTSMulticompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state.CONCLUSIONOur data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9–124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-2H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day−1 was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day−1 (P=0.03). Our data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. Abstract Objectives Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). Materials and Methods The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9–124.7 nmol/L]. All subjects received a primed constant infusion of [5,5,5-2 H3 ] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry. Results Multicompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively ( P = 0.04). The median Lp(a) apo(a) production rate at 0.248 nmol/kg · day − 1 was significantly lower than that of Lp(a) apoB-100 at 0.514 nmol/kg · day − 1 ( P = 0.03). Conclusion Our data indicate that apo(a) has a plasma residence time (11 days) that is more than twice as long as that of apoB-100 (4 days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state. |
| Author | Diffenderfer, Margaret R. Schaefer, Ernst J. Barrett, P. Hugh R. Marcovina, Santica M. Lamon-Fava, Stefania Lel, Julian Dolnikowski, Gregory G. Berglund, Lars |
| Author_xml | – sequence: 1 givenname: Margaret R. surname: Diffenderfer fullname: Diffenderfer, Margaret R. email: margaret.diffenderfer@tufts.edu organization: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA – sequence: 2 givenname: Stefania surname: Lamon-Fava fullname: Lamon-Fava, Stefania email: stefania.lamon-fava@tufts.edu organization: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA – sequence: 3 givenname: Santica M. surname: Marcovina fullname: Marcovina, Santica M. email: smm@uw.edu organization: Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, 401 Queen Anne Avenue North, Seattle, WA 98109, USA – sequence: 4 givenname: P. Hugh R. surname: Barrett fullname: Barrett, P. Hugh R. email: hugh.barrett@uwa.edu.au organization: School of Medicine and Pharmacology and Faculty of Engineering, Computing and Mathematics, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia – sequence: 5 givenname: Julian orcidid: 0000-0001-8564-8137 surname: Lel fullname: Lel, Julian email: julian.lel@gmail.com organization: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA – sequence: 6 givenname: Gregory G. surname: Dolnikowski fullname: Dolnikowski, Gregory G. email: gregory.dolnikowski@tufts.edu organization: Mass Spectrometry Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA – sequence: 7 givenname: Lars surname: Berglund fullname: Berglund, Lars email: lars.berglund@ucdmc.usdavis.edu organization: Clinical and Translational Science Center, University of California, Davis, 2921 Stockton Boulevard, Suite 1400, Sacramento, CA 95817, USA – sequence: 8 givenname: Ernst J. surname: Schaefer fullname: Schaefer, Ernst J. email: ernst.schaefer@tufts.edu organization: Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA |
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| Keywords | apo PR PAS PS d PCSK9 Lp(a) TC IDL Lipoprotein(a) TG FCR Fed state Hypertriglyceridemia VLDL KIV2 KIV1 Kinetics CHD GC/MS apolipoprotein gas chromatography/mass spectrometry intermediate density lipoprotein ( d 1.006–1.019 g/mL) KIV 2 KIV 1 total cholesterol fractional catabolic rate periodic acid Schiff's base kringle IV 2 kringle IV 1 proprotein convertase subtilisin/kexin type 9 density production rate triglycerides pool size coronary heart disease very low-density lipoprotein ( d < 1.006 g/mL) lipoprotein(a) |
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| Snippet | Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was... Abstract Objectives Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to... Objectives: Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our... |
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| SubjectTerms | Apolipoprotein B-100 - biosynthesis Apolipoprotein B-100 - blood Apolipoprotein B-100 - metabolism Apolipoproteins A - biosynthesis Apolipoproteins A - metabolism Dyslipidemias - blood Endocrinology & Metabolism Fed state Humans Hypertriglyceridemia Hypertriglyceridemia - metabolism Kinetics Leucine - metabolism Lipids - blood Lipoprotein(a) Lipoprotein(a) - biosynthesis Lipoprotein(a) - metabolism Male Middle Aged |
| Title | Distinct metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein(a) |
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