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Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

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Lipids

Abstract

Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A-I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with 3H-cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA-I KO than in WT. In apoA-I transgenic mice, LDE clearance was lower than in apoA-I KO and than in apoA-I KO infusion with human HDL. Infusion of human HDL into the apoA-I KO mice resulted in higher LDE clearance than in the apoA-I transgenic mice (p < 0.05). In apoA-I KO and apoA-I KO infused human HDL, the liver uptake was greater than in WT animals and apoA-I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A-I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA-I also influences those processes.

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Abbreviations

3H–CE:

3H-cholesteryl ether

apoA-I:

Apolipoprotein A-I

apoB100:

Apolipoprotein B100

apoE/A-I:

Apolipoprotein E/apolipoprotein A-I

apoE3:

Apolipoprotein E3

apoE:

Apolipoprotein E

KO:

Knockout

LDL:

Low density lipoprotein

LDLR:

Low density lipoprotein receptor

SR-BI:

Scavenger receptor class B type I

WT:

Wild type

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Acknowledgements

The authors thank Gayle Forbes (in memoriam) (Boston University) for technical assistance.

Author information

Authors and Affiliations

  1. Heart Institute (InCor) of the Medical School Hospital, FMUSP, University of São Paulo, São Paulo, SP, Brazil

    Elaine N. Daminelli, Carlos H. Mesquita & Raul C. Maranhão

  2. Departments of Medicine and Biochemistry, Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA

    Elaine N. Daminelli, Panagiotis Fotakis & Vassilis I. Zannis

  3. Department of Biochemistry, University of Crete Medical School, Crete, Greece

    Panagiotis Fotakis & Vassilis I. Zannis

  4. Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil

    Raul C. Maranhão

Authors
  1. Elaine N. Daminelli
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  2. Panagiotis Fotakis
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  3. Carlos H. Mesquita
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  4. Raul C. Maranhão
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  5. Vassilis I. Zannis
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Corresponding author

Correspondence to Raul C. Maranhão.

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Funding

This study was supported by National Council for Scientific and Technological Development (CNPq, Brasília, Brazil; Grant 473031/2012-4), São Paulo State Research Support Foundation (FAPESP, São Paulo, Brazil; Grant 14/03742-0), and Boston University (Boston, MA, USA). Dr. Maranhão has a Research Carrier Award from CNPq.

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The authors declare they have no conflicts of interest.

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Daminelli, E.N., Fotakis, P., Mesquita, C.H. et al. Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice. Lipids 52, 991–998 (2017). https://doi.org/10.1007/s11745-017-4306-6

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  • DOI: https://doi.org/10.1007/s11745-017-4306-6

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