Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation
Por:
Rull, A, Jayaraman, S, Gantz, DL, Rivas-Urbina, A, Perez-Cuellar, M, Ordonez-Llanos, J, Sanchez-Quesada, JL, Gursky, O
Publicada:
1 sep 2016
Resumen:
Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(-), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(-). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(-) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(-) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and an increase in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(-). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(-) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL( +), LDL(-) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoj had an opposite effect. Therefore, the initial rapid aggregation of LDL(-) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoj. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo. (C) 2016 Elsevier B.V. All rights reserved.
Filiaciones:
Rull, A:
Res Inst Hosp St Pau IIB St Pau, Cardiovasc Biochem Grp, C Antoni Maria Claret,167, Barcelona 08025, Spain
Jayaraman, S:
Boston Univ, Sch Med, Dept Physiol & Biophys, 700 Albany St, Boston, MA 02118 USA
Gantz, DL:
Boston Univ, Sch Med, Dept Physiol & Biophys, 700 Albany St, Boston, MA 02118 USA
Rivas-Urbina, A:
Res Inst Hosp St Pau IIB St Pau, Cardiovasc Biochem Grp, C Antoni Maria Claret,167, Barcelona 08025, Spain
Univ Autonoma Barcelona, Biochem & Mol Biol Dept, Cerdanyola Del Valles, Spain
Perez-Cuellar, M:
Res Inst Hosp St Pau IIB St Pau, Cardiovasc Biochem Grp, C Antoni Maria Claret,167, Barcelona 08025, Spain
Ordonez-Llanos, J:
Res Inst Hosp St Pau IIB St Pau, Cardiovasc Biochem Grp, C Antoni Maria Claret,167, Barcelona 08025, Spain
Univ Autonoma Barcelona, Biochem & Mol Biol Dept, Cerdanyola Del Valles, Spain
Sanchez-Quesada, JL:
Res Inst Hosp St Pau IIB St Pau, Cardiovasc Biochem Grp, C Antoni Maria Claret,167, Barcelona 08025, Spain
Gursky, O:
Boston Univ, Sch Med, Dept Physiol & Biophys, 700 Albany St, Boston, MA 02118 USA
Green Accepted
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