Margaret R Diffenderfer1, Stefania Lamon-Fava2, Santica M Marcovina3, P Hugh R Barrett4, Julian Lel5, Gregory G Dolnikowski6, Lars Berglund7, Ernst J Schaefer8. 1. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: margaret.diffenderfer@tufts.edu. 2. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: stefania.lamon-fava@tufts.edu. 3. Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, 401 Queen Anne Avenue North, Seattle, WA 98109, USA. Electronic address: smm@uw.edu. 4. School of Medicine and Pharmacology and Faculty of Engineering, Computing and Mathematics, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Electronic address: hugh.barrett@uwa.edu.au. 5. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: julian.lel@gmail.com. 6. Mass Spectrometry Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: gregory.dolnikowski@tufts.edu. 7. Clinical and Translational Science Center, University of California, Davis, 2921 Stockton Boulevard, Suite 1400, Sacramento, CA 95817, USA. Electronic address: lars.berglund@ucdmc.usdavis.edu. 8. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: ernst.schaefer@tufts.edu.
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: 8.9-124.7nmol/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. 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 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03). CONCLUSION: 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: 8.9-124.7nmol/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. 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 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a)apoB-100 at 0.514nmol/kg·day(-1) (P=0.03). CONCLUSION: 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.
Authors: Justin R Clark; Matthew Gemin; Amer Youssef; Santica M Marcovina; Annik Prat; Nabil G Seidah; Robert A Hegele; Michael B Boffa; Marlys L Koschinsky Journal: J Lipid Res Date: 2022-04-22 Impact factor: 6.676
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